Merck Manual

Please confirm that you are a health care professional

Loading

Immunotherapeutics

By

Peter J. Delves

, PhD, University College London, London, UK

Last full review/revision Apr 2020| Content last modified Apr 2020
Click here for Patient Education
NOTE: This is the Professional Version. CONSUMERS: Click here for the Consumer Version
Topic Resources

Immunotherapeutic agents use or modify immune mechanisms. Use of these agents is rapidly evolving; new classes, new agents, and new uses of current agents are certain to be developed. A number of different classes of immunotherapeutic agents have been developed (see also table Some Immunotherapeutic Agents in Clinical Use):

  • Monoclonal antibodies

  • Fusion proteins

  • Soluble cytokine receptors

  • Recombinant cytokines

  • Small-molecule mimetics

  • Cellular therapies

Table
icon

Some Immunotherapeutic Agents in Clinical Use

Agent

Effects

Some Indications

Monoclonal antibodies*

Abciximab

Antiglycoprotein IIb/IIIa receptor

Prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention or in some high-risk patients with acute coronary syndrome

Adalimumab

Anti–TNF-alpha

Moderate to severe hidradenitis suppurativa

Moderate to severe Crohn disease refractory to standard treatments

Moderate to severe polyarticular juvenile idiopathic arthritis

Moderate to severe rheumatoid arthritis

Moderate to severe ulcerative colitis refractory to standard treatments

Non-infectious intermediate, posterior, and pan uveitis

Moderate to severe chronic plaque psoriasis

Alemtuzumab

Anti–B cell (CD52)

B-cell CLL refractory to standard treatments

Relapsing multiple sclerosis in patients who have had an inadequate response to ≥ 2 drugs

Alirocumab

Anti-proprotein convertase subtilisin kexin type 9

Lowering of LDL cholesterol, as an adjunct to diet and statins, in adults with heterozygous familial hypercholesterolemia or atherosclerotic cardiovascular disease

Atezolizumab

Anti–PD-L1

Locally advanced or metastatic transitional cell (urothelial) carcinoma

Metastatic NSCLC

Extensive-stage small cell lung cancer

Locally advanced or metastatic triple-negative breast cancer

Avelumab 

Anti-PD-L1

Locally advanced or metastatic urothelial carcinoma in patients with disease progression during or following platinum-based chemotherapy

Basiliximab

Anti–IL-2 receptor

Prevention of acute rejection of a transplanted kidney

Belimumab

Anti–B-lymphocyte stimulator protein (anti-BLyS)

Autoantibody-positive systemic lupus erythematosus in adults receiving standard treatment

Benralizumab

Anti-IL-5 receptor alpha

Add-on maintenance treatment of patients aged ≥ 12 years with severe eosinophilic asthma

Bevacizumab

Anti–VEGF-A

Epithelial ovarian, fallopian tube, or primary peritoneal cancer (used with paclitaxel, pegylated liposomal doxorubicin, or topotecan in patients with platinum-resistant recurrent disease who received no more than 2 prior chemotherapy regimens; with carboplatin and paclitaxel, followed by bevacizumab as a single agent, for stage III or IV disease following initial surgical resection; in combination with carboplatin and paclitaxel or carboplatin and gemcitabine, followed by bevacizumab as a single agent, for platinum-sensitive recurrent disease)

Glioblastoma in adults if the disorder progresses after other treatments have been tried

Metastatic colorectal cancer (used with IV 5-fluorouracil–based chemotherapy as first- or 2nd-line treatment)

Metastatic colorectal cancer (used with fluoropyrimidine–irinotecan– or fluoropyrimidine-oxaliplatin–based chemotherapy as 2nd-line treatment) if the cancer progressed during treatment with a first-line regimen that contains bevacizumab

Metastatic renal cell carcinoma (used with IFN-alpha)

Persistent, recurrent, or metastatic cervical cancer (used with paclitaxel and cisplatin, or paclitaxel and topotecan)

Unresectable, locally advanced, recurrent, or metastatic nonsquamous NSCLC (used with carboplatin and paclitaxel as first-line treatment)

Bezlotoxumab

Anti-Clostridioides (formerly, Clostridium) difficile toxin B

C. difficile infection in adults receiving antibiotics and at high risk of recurrence

Blinatumomab

Bispecific: Anti-CD19 and anti-CD3c

Relapsed or refractory B-cell precursor ALL

B-cell precursor ALL in 1st or 2nd complete remission with MRD ≥ 0.1%

Brentuximab vedotin

Anti-CD30 (linked to the antimitotic agent monomethyl auristatin E)

Previously untreated stage III or IV Hodgkin lymphoma (used with doxorubicin, vinblastine, and dacarbazine)

Hodgkin lymphoma at high risk of relapse or progression at post-ASCT consolidation

Hodgkin lymphoma after failure of ASCT or of at least 2 multidrug chemotherapy regimens in patients who are not candidates for ASCT

Previously untreated systemic ALCL or other CD30-expressing peripheral T cell lymphomas (used with cyclophosphamide, doxorubicin, and prednisone)

Systemic ALCL after failure of at least one multidrug chemotherapy regimen

Primary cutaneous ALCL or CD30-expressing mycosis fungoides in patients who have received prior systemic therapy

Brodalumab

Anti-IL-17 receptor A

Moderate to severe plaque psoriasis in adults not responding to other systemic therapies

Brolucizumab

Anti-VEGF-A

Burosumab

Anti-fibroblast growth factor 23

X-linked hypophosphatemia in adults and pediatric patients ≥ 6 months

Canakinumab

Anti–IL-1 beta

Active systemic juvenile idiopathic arthritis in patients ≥ 2 years

Gout in patients that have not responded adequately to treatment with NSAIDs or colchicine, or with contraindications or intolerances to those drugs, and in whom repeated courses of corticosteroids are inappropriate

Periodic fever syndromes:

Caplacizumab

Anti-von Willibrand factor

Adult patients with acquired thrombotic thrombocytopenic purpura (used with plasma exchange and immunosuppressive therapy)

Cemiplimab

Anti-PD-1

Metastatic or locally advanced cutaneous squamous cell carcinoma in patients who are not candidates for curative surgery or curative radiation therapy

Certolizumab (pegylated Fab’ fragment)

Anti–TNF-alpha

Moderate to severe Crohn disease if response to conventional treatments is inadequate

Moderate to severe plaque psoriasis 

Moderate to severe rheumatoid arthritis in adults

Nonradiographic axial spondyloarthritis with objective signs of inflammation

Cetuximab

Anti-EGFR

Locally or regionally advanced HNSCC (used with radiation therapy)

Recurrent locoregional or metastatic HNSCC (used with platinum-based therapy and 5-fluorouracil)

Recurrent or metastatic HNSCC if it progresses after platinum-based therapy

K-Ras wild-type, EGFR-expressing metastatic colorectal cancer: Given as follows:

  • With FOLFIRI as first-line treatment

  • With irinotecan if the cancer is refractory to irinotecan-based chemotherapy

  • As a single agent if oxaliplatin- and irinotecan-based chemotherapy is ineffective or patients cannot tolerate irinotecan

Crizanlizumab

Anti-P-selectin

Daratumumab

Anti-CD38

  • As monotherapy if patients have received ≥ 3 prior drug regimens that included a proteasome inhibitor and an immunomodulatory drug

    or

  • As monotherapy if the cancer is refractory to both a proteasome inhibitor and an immunomodulatory drug

    In combination with lenalidomide and dexamethasone in newly diagnosed patients ineligible for ASCT and in patients with relapsed or refractory disease who have received ≥ 1 prior drug regimens

    In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients ineligible for ASCT

    In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for ASCT

    In combination with bortezomib and dexamethasone in patients who have received ≥ 1 prior drug regimens

    In combination with pomalidomide and dexamethasone in patients who have received ≥ 2 prior drug regimens that included lenalidomide and a proteasome inhibitor

Denosumab

Anti-RANKL

Prevention of skeletal-related events (eg, fractures, bone pain) in patients with multiple myeloma or bone metastases from solid tumors

Treatment of adults and skeletally mature adolescents with a giant cell tumor of bone if the tumor is unresectable or if surgical resection is likely to result in severe morbidity

Treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy

Osteoporosis in patients at high risk of fracture

To increase bone mass in men receiving androgen deprivation therapy for nonmetastatic prostate cancer and in women receiving adjuvant aromatase inhibitor therapy for breast cancer at high risk of fracture

Dinutuximab

Anti-GD2 glycolipid

High-risk pediatric neuroblastoma that has at least partially responded to prior first-line multidrug, multimodality therapy (used with GM-CSF, IL-2, and isotretinoin [13-cis-retinoic acid])

Dupilumab

Anti-IL-4 receptor alpha

Moderate to severe atopic dermatitis in patients ≥ 12 years when disease is not adequately controlled with topical therapies or when those therapies are not advisable

Moderate to severe atopic asthma in patients ≥ 12 years with an eosinophilic phenotype or with oral corticosteroid dependent asthma

Add-on maintenance treatment in adults with inadequately controlled chronic rhinosinusitis with nasal polyposis

Durvalumab

Anti-PD-L1

Locally advanced or metastatic urothelial carcinoma with disease progression during or following platinum-based chemotherapy, or within 12 months of neoadjuvant or adjuvant treatment with platinum-based chemotherapy

Unresectable stage III NSCLC when disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy

Eculizumab

Anti–complement component C5

Elotuzumab

Anti-SLAMF7

Multiple myeloma in patients who have received 1 to 3 prior therapies (used with lenalidomide and dexamethasone) or ≥ 2 prior therapies including lenalidomide and a proteasome inhibitor (used with pomalidomide and dexamethasone)

Emapalumab

Anti-IFN-gamma

Emicizumab

Bispecific anti-factor IXa and anti-factor X

Prevention or reduction of bleeding episodes in patients with hemophilia A with or without factor VIII inhibitors

Enfortumab vedotin

Anti-Nectin-4 linked to the antimitotic drug monomethyl auristatin E

Locally advanced or metastatic urothelial cancer in patients who have previously received neoadjuvant/adjuvant PD-1 or PD-L1 inhibitor and platinum-based chemotherapy

Erenumab

Anti- calcitonin gene-related peptide receptor

Migraine prevention

Evolocumab

Anti-proprotein convertase subtilisin kexin type 9

Cardiovascular risk reduction in patients with coronary artery disease

Lowering of LDL-cholesterol, as an adjunct to diet and statins (and other LDL-lowering therapies), in adults with homozygous or heterozygous familial hypercholesterolemia or atherosclerotic cardiovascular disease

Fremanezumab

Anti- calcitonin gene-related peptide receptor

Migraine prevention

Galcanezumab

Anti- calcitonin gene-related peptide receptor

Migraine prevention

Gemtuzumab

Anti-CD33 ozogamicin conjugate

Newly-diagnosed CD33+ acute myeloid leukemia in adults, or relapsed or refractory disease in adults and children ≥ 2 years

Golimumab

Anti–TNF-alpha

Moderate to severe rheumatoid arthritis (used with methotrexate)

Psoriatic arthritis (alone or in combination with methotrexate)

Moderate to severe ulcerative colitis if

  • Patients have an inadequate response to or are intolerant of prior treatments

    or

  • They require continuous corticosteroid therapy

Guselkumab

Anti-IL-23

Moderate to severe plaque psoriasis

Ibalizumab

Anti-CD4

Human immunodeficiency virus (HIV) type 1 infection (used with other antiretroviral(s) in heavily treatment-experienced adults with multidrug resistant infection)

Ibritumomab tiuxetan

Anti–CD20 linked to the radioactive agent yttrium 90

Low-grade or follicular B-cell non-Hodgkin lymphoma that has relapsed during or after treatment with other anticancer drugs

Newly diagnosed follicular B-cell non-Hodgkin lymphoma following a response to initial anticancer therapy

Idarucizumab

Anti-dabigatran

Reversal of the anticoagulant effects of dabigatran etexilate when needed for emergency surgery/urgent procedures or in life-threatening or uncontrolled bleeding

Infliximab

Anti–TNF-alpha

Moderate to severe Crohn disease or ulcerative colitis if response to conventional treatments is inadequate

Moderate to severe rheumatoid arthritis (used with methotrexate)

Chronic severe plaque psoriasis when other treatments are less appropriate

Inotuzumab

Anti-CD22-ozogamicin conjugate

Adults with relapsed or refractory B-cell precursor ALL

Ipilimumab

Anti–CTLA-4

Inoperable or metastatic melanoma in patients aged ≥ 12 years 

Melanoma with pathologic involvement of regional lymph nodes of > 1 mm in patients who have had complete resection, including total lymphadenectomy

Previously untreated advanced renal cell carcinoma (used with nivolumab)

MSI-H or dMMR metastatic colorectal cancer  that has progressed after treatment with a fluoropyrimidine, oxaliplatin, and irinotecan (used with nivolumab) in patients aged ≥ 12 years

Isatuximab

Anti-CD38

In combination with pomalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor

Ixekizumab

Anti-IL17A

Moderate to severe plaque psoriasis

Lanadelumab

Anti-plasma kallikrein

Prevention of recurrent attacks of hereditary angioedema in patients ≥ 12 years

Mepolizumab

Anti-IL-5

Add-on maintenance treatment for severe eosinophilic asthma in patients aged ≥ 6 years 

Mogamulizumab

Anti-CCR4

Adult patients with relapsed or refractory mycosis fungoides or Sezary syndrome after ≥ 1 prior systemic therapies

Moxetumomab pasudotox

Anti-CD22 linked to a truncated form of Pseudomonas exotoxin PE38

Adult patients with relapsed or refractory hairy cell leukemia who received ≥ 2 prior systemic therapies including treatment with a purine nucleoside analog

Natalizumab

Anti–alpha-4 integrin subunit

Relapsing multiple sclerosis or Crohn disease when other treatments are inadequate

Necitumumab

EGFR1

Metastatic squamous NSCLC as first-line treatment (used with gemcitabine and cisplatin)

Nivolumab

Anti–PD-1

Unresectable or metastatic melanoma (used with ipilimumab and, if the melanoma is BRAF V600 mutation–positive, with a BRAF inhibitor)

Metastatic NSCLC if it progresses during or after platinum-based chemotherapy

Advanced renal cell carcinoma in patients who have received prior antiangiogenesis therapy or in untreated patients if given in combination with ipilimumab

Hodgkin lymphoma that recurs or progresses after ASCT and post-transplantation treatment with brentuximab vedotin, or after ≥ 3 lines of systemic therapy, including autologous ASCT 

Recurrent or metastatic HNSCC with disease progression on or after platinum-based therapy

Locally advanced or metastatic urothelial carcinoma with disease progression on or after platinum-based therapy

MSI-H or dMMR metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan

Hepatocellular carcinoma previously treated with sorafenib

Obiltoxaximab

Anti-protective antigen of Bacillus anthracis

Inhalational anthrax (used with antibiotics)

Obinutuzumab

Anti-CD20

Follicular lymphoma that recurred after or is refractory to a regimen that contains rituximab (used first with bendamustine, then given as monotherapy)

Adult patients with previously untreated stage II bulky, stage III, or stage IV follicular lymphoma (used with chemotherapy followed by obinutuzumab monotherapy in patients achieving at least a partial remission)

Previously untreated CLL (used with chlorambucil)

Ocrelizumab

Anti-CD20

Relapsing or primary progressive forms of multiple sclerosis

Ofatumumab

Anti‒CD20

Previously untreated CLL in patients for whom fludarabine-based therapy is considered inappropriate (used with chlorambucil)

Extended treatment of CLL in patients with complete or partial response after ≥ 2-drug regimens for recurrent or progressive disease

CLL refractory to fludarabine and alemtuzumab

Relapsed CLL (used with fludarabine and cyclophosphamide)

Omalizumab

Anti-IgE

Moderate to severe asthma in patients > 6 years with documented allergic disorders inadequately controlled by inhaled corticosteroids

Chronic idiopathic urticaria in patients ≥ 12 years who remain symptomatic despite H1 antihistamine treatment

Palivizumab

Anti-respiratory syncytial virus (RSV) F protein

Serious lower respiratory tract RSV infection in children

Panitumumab

Anti-EGFR

Wild-type RAS metastatic colorectal cancer as first-line treatment used with FOLFOX, or as monotherapy if cancer progresses after prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan

Pembrolizumab

Anti–PD-1

Inoperable or metastatic advanced melanoma

Adjuvant treatment of melanoma with involvement of lymph nodes following complete resection

PD-L1+ NSCLC as a single agent for first-line treatment in patients with no EGFR or ALK genomic tumor aberrations

As a single agent for the treatment of patients with metastatic PD-L1+ NSCLC with disease progression on or after platinum-based chemotherapy (patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab)

First-line treatment of metastatic nonsquamous NSCLC in patients with no EGFR or ALK genomic tumor aberrations (used with pemetrexed and carboplatin)

First-line treatment of metastatic squamous NSCLC (used with paclitaxel and carboplatin)

Metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy and at least one other line of therapy

Recurrent or metastatic HNSCC with disease progression on or after platinum-based chemotherapy

First line treatment of metastatic or unresectable recurrent HNSCC (used with fluorouracil and platinum-based chemotherapy)

First-line treatment of PD-L1+ metastatic or unresectable recurrent HNSCC

Hodgkin lymphoma patients with refractory disease or who have relapsed after ≥ 3 prior lines of therapy

Primary mediastinal large B-cell lymphoma patients with refractory disease or who have relapsed after ≥ 2 prior lines of therapy

PD-L1+ locally advanced or metastatic urothelial carcinoma in patients ineligible for cisplatin-containing chemotherapy, or who are ineligible for any platinum-based chemotherapy regardless of PD-L1 status, or who have disease progression during or following platinum-based chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-based chemotherapy

Unresectable or metastatic MSI-H/dMMR solid tumors, regardless of type, that have progressed following prior treatment in patients who have no satisfactory alternative treatment options

Colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan

PD-L1+ recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma with disease progression on or after ≥ 2 prior lines of therapy including fluoropyrimidine- and platinum-based chemotherapy and, if appropriate, HER2/neu-targeted therapy

PD-L1+ recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus with disease progression after ≥ 1 prior lines of systemic therapy

PD-L1+ recurrent or metastatic cervical cancer with disease progression on or after chemotherapy

Hepatocellular carcinoma previously treated with sorafenib

Recurrent locally advanced or metastatic Merkel cell carcinoma

First line treatment of advanced renal cell carcinoma (used with axitinib)

Advanced endometrial carcinoma that does not have microsatellite instability in multiple regions (MSI-H) or dMMR in patients who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation therapy (used with lenvatinib)

Pertuzumab

Anti-HER2

HER2+ metastatic breast cancer in patients who have not received prior anti-HER2 therapy or chemotherapy for metastatic cancer (used with trastuzumab and docetaxel)

HER2+, locally advanced, inflammatory, or early-stage breast cancer (either > 2 cm in diameter or node-positive) for neoadjuvant treatment (used with trastuzumab and docetaxel) as part of a complete treatment regimen for early breast cancer

Polatuzumab

Anti-CD79b

Relapsed or refractory diffuse large B-cell lymphoma after ≥ 2 prior therapies (used with bendamustine and rituximab)

Ramucirumab

Anti–VEGFR-2

Metastatic colorectal cancer that has progressed during or after a first-line drug regimen that contains bevacizumab, oxaliplatin, and a fluoropyrimidine (used with FOLFIRI)

Metastatic NSCLC that progressed during or after platinum-based chemotherapy (used with docetaxel)

Advanced or metastatic gastric or gastroesophageal junction adenocarcinoma if it progresses during or after prior chemotherapy that contains a fluoropyrimidine or platinum-containing drug (used alone or with paclitaxel)

Hepatocellular carcinoma with alpha-fetoprotein level ≥ 400 ng/mL (> 400 microgram/L) and treated with sorafenib

Ranibizumab

Anti-VEGF

Macular edema after retinal vein occlusion

Diabetic macular edema

Myopic choroidal neovascularization 

Ravulizumab

Anti-C5

Adults and children with atypical hemolytic uremic syndrome

Raxibacumab

Anti-protective antigen of Bacillus anthracis

Inhalational anthrax (used with antibiotics)

Reslizumab

Anti-IL-5

Add-on maintenance treatment for severe eosinophilic asthma in patients aged ≥ 18 years

Risankizumab

Anti-IL-23p19

Moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy

Rituximab

Anti–CD20

Relapsed or refractory CD20+, low-grade or follicular B-cell non-Hodgkin lymphoma

CD20+ CLL (used with fludarabine and cyclophosphamide)

Moderate to severe rheumatoid arthritis (used with methotrexate) when response to TNF-antagonists is inadequate

Moderate to severe pemphigus vulgaris 

Romosozumab

Anti-sclerostin

Postmenopausal osteoporosis in women at high risk for fracture or patients in whom other available osteoporosis therapy has failed or cannot be tolerated

Sarilumab

Anti-IL-6 receptor

Adult with moderate to severe rheumatoid arthritis who have had an inadequate response or intolerance to one or more DMARDs

Secukinumab

Anti–IL-17A

Moderate to severe plaque psoriasis

Siltuximab

Anti–IL-6

Multicentric Castleman disease in patients who are HIV- and HHV-8–negative

Teprotumumab

Anti-IGF-1 receptor

Thyroid eye disease

Tildrakizumab

Anti-IL-23

Adults with moderate to severe plaque psoriasis

Tocilizumab

Anti–IL-6 receptor

Moderate to severe rheumatoid arthritis when response to at least one DMARD is inadequate

Polyarticular or systemic juvenile idiopathic arthritis in patients ≥ 2 years

Patients ≥ 2 years who experience severe or life-threatening cytokine release syndrome following CAR T cell treatment 

Tositumomab

Anti–CD20 linked to radioactive iodine [131I]

Refractory and relapsed CD20+ low-grade follicular or transformed non-Hodgkin lymphoma that has progressed during or after rituximab therapy

Trastuzumab

Anti–HER2

HER2+ metastatic stomach or gastroesophageal junction adenocarcinoma

Ustekinumab

Anti–IL-12 and –IL-23

Moderate to severe plaque psoriasis

Moderate to severe Crohn disease

Moderate to severe ulcerative colitis

Vedolizumab

Anti–alpha-4 beta-7 integrin

Moderate to severe active ulcerative colitis if response to conventional therapy or TNF-antagonists is inadequate

Moderate to severe Crohn disease if response to conventional therapy or TNF-antagonists is inadequate

Fusion proteins

Abatacept (CTLA-4 extracellular domain fused to the Fc region of IgG1)

Inhibition of T-cell activation

Moderate to severe rheumatoid arthritis

Moderate to severe polyarticular juvenile idiopathic arthritis in patients ≥ 2 years

Denileukin diftitox (fusion of IL-2 to diphtheria toxin)

Delivery of toxin to CD25 component of IL-2 receptor

CD25+ cutaneous T-cell lymphoma

Etanercept (fusion of 2 CD120b TNF-alpha receptors to Fc region of IgG1)

Decrease in TNF levels

Polyarticular juvenile idiopathic arthritis in patients ≥ 2 years

Soluble cytokine receptor

Anakinra (IL-1 receptor antagonist, sometimes pegylated for longer half-life)

Competitive inhibition of IL-1 alpha and IL-1 beta activities

Moderate to severe rheumatoid arthritis in patients 18 years

Cytokines

IFN-alpha

Antiproliferative and antiviral

Chronic hepatitis B in patients 3 years

Chronic hepatitis C in patients ≥ 5 years

In patients 18 years:

IFN-beta

Antiproliferative and antiviral

Reduction of number of flare-ups in relapsing multiple sclerosis

IFN-gamma

Immunostimulatory and antiviral

Control of infection in chronic granulomatous disease, delay of progression in severe malignant osteopetrosis

IL-2

Immunostimulatory

Metastatic renal cell carcinoma and metastatic melanoma

IL-11

Thrombopoietic growth factor

Prevention of thrombocytopenia after myelosuppressive chemotherapy

G-CSF

Stimulation of granulocyte production

Reversal of neutropenia after chemotherapy or transplantation for hematologic disorders or cancer

Patients with severe chronic neutropenia

GM-CSF

Stimulation of granulocyte and monocyte/macrophage production

Reversal of neutropenia after chemotherapy or transplantation for hematologic disorders or cancer

Patients with severe chronic neutropenia

Cellular therapy

Axicabtagene ciloleucel (CAR T)

CD19-directed genetically modified autologous T-cell

Adults with relapsed or refractory large B-cell lymphoma after 2 lines of systemic therapy

Sipuleucel-T

Autologous circulating ICAM-1+ peripheral blood mononuclear cells activated with prostatic acid phosphatase and GM-CSF

Asymptomatic or minimally symptomatic metastatic prostate cancer refractory to castration (hormone therapy)

Tisagenlecleucel (CAR T)

CD19-directed genetically modified autologous T-cell

Patients up to 25 years with B-cell precursor ALL that is refractory or in second or later relapse

Adults with relapsed or refractory large B-cell lymphoma after 2 lines of systemic therapy

* mAbs used for diagnostic testing and radiologic imaging are not included. The Antibody Society maintains a comprehensive list of approved antibody therapeutics and those in regulatory review in the United States and the European Union.

ALCL = anaplastic large cell lymphoma; ALL = acute lymphoblastic leukemia; ANCA = antineutrophil cytoplasmic antibodies; ASCT = autologous stem cell transplantation; CAR = chimeric antigen receptor; CD = cluster of differentiation; CLL = chronic lymphocytic leukemia; CTLA = cytotoxic T-lymphocyte antigen; DMARD = disease-modifying antirheumatic drugs; dMMR = DNA mismatch repair deficient; EGFR = epidermal growth factor receptor; Fc = crystallizable fragment; FOLFIRI = leucovorin (folinic acid), fluorouracil, plus irinotecan; FOLFOX = leucovorin (folinic acid), fluorouracil, plus oxaliplatin; G-CSF = granulocyte colony-stimulating factor; GM-CSF = granulocyte-macrophage colony-stimulating factor; HER2 = human epidermal growth factor receptor 2; HHV-8 = human herpesvirus 8; HNSCC = head and neck squamous cell carcinoma; ICAM = intercellular adhesion molecule; IFN = interferon; IL = interleukin; LDL = low density lipoprotein; mAb = monoclonal antibody; MRD = minimal residual disease; MSI-H = microsatellite instability-high; NSCLC = non small cell lung cancer; PD-L1 = programmed death–ligand 1; RANKL = receptor activator of nuclear factor kappa beta ligand; SLAMF7 = signaling lymphocyte activation molecule family member 7; TNF = tumor necrosis factor; VEGF-A = vascular endothelial growth factor A; VEGFR = VEGF receptor.

Monoclonal antibodies

Monoclonal antibodies (mAbs) are manufactured in vitro to recognize specific targeted antigens (Ags); they are used to treat solid and hematopoietic tumors and inflammatory disorders. The monoclonal antibodies that are currently in clinical use include

  • Murine

  • Chimeric

  • Humanized

  • Fully human

Murine monoclonal antibodies are produced by injecting a mouse with an antigen, harvesting its spleen to obtain B cells that are producing antibody specific to that antigen, fusing those cells with immortal mouse myeloma cells, growing these hybridoma cells (eg, in cell culture), and harvesting the antibody. Although mouse antibodies are similar to human antibodies, clinical use of murine monoclonal antibodies is limited because they induce human anti-mouse antibody production, can cause immune complex serum sickness (a type III hypersensitivity reaction), and are rapidly cleared.

To minimize the problems due to use of pure mouse antibody, researchers have used recombinant DNA techniques to create monoclonal antibodies that are part human and part mouse. Depending on the proportion of the antibody molecule that is human, the resultant product is termed one of the following:

  • Chimeric

  • Humanized

In both cases, the process usually begins as above with production of mouse hybridoma cells that make antibody to the desired antigen. Then the DNA for some or all of the variable portion of the mouse antibody is merged with DNA for human immunoglobulin. The resultant DNA is placed in a mammalian cell culture, which then expresses the resultant gene, producing the desired antibody. If the mouse gene for the whole variable region is spliced next to the human constant region, the product is termed "chimeric." If the mouse gene for only the antigen-binding hypervariable regions of the variable region is used, the product is termed "humanized."

Chimeric monoclonal antibodies activate antigen-presenting cells (APCs) and T cells more effectively than murine monoclonal antibodies but can still induce production of human anti-chimeric antibodies.

Humanized monoclonal antibodies against various antigens are available for the treatment of colorectal cancer, breast cancer, leukemia, allergy, autoimmune disease, transplant rejection, and respiratory syncytial virus infection.

Fully human monoclonal antibodies are produced using transgenic mice that contain human immunoglobulin genes or using phage display (ie, a bacteriophage-based cloning method) of immunoglobulin genes isolated from human B cells. Fully human monoclonal antibodies have decreased immunogenicity and therefore may have fewer adverse effects in patients.

Monoclonal antibodies that target checkpoint molecules on either T cells or tumor cells (termed checkpoint inhibitors—see table Some Immunotherapeutic Agents in Clinical Use) are used to prevent downregulation of antitumor responses and effectively treat some heretofore resistant cancers. However, because checkpoint molecules are also involved in other types of immune response, checkpoint inhibitors can cause severe immune-related inflammatory and autoimmune reactions (both systemic and organ specific).

Fusion proteins

These hybrid proteins are created by linking together the gene sequences encoding all or part of 2 different proteins to generate a chimeric polypeptide that incorporates desirable attributes from the parent molecules (eg, a cell-targeting component combined with a cell toxin). The circulating half-life of therapeutic proteins can also often be improved by fusing them to another protein that naturally has a longer serum half-life (eg, the Fc region of IgG).

Soluble cytokine receptors

Soluble versions of cytokine receptors are used as therapeutic reagents. They can block the action of cytokines by binding with them before they attach to their normal cell surface receptor.

Etanercept, a fusion protein, consists of 2 identical chains from the CD120b receptor for tumor necrosis factor (TNF)-alpha. This agent thus blocks TNF-alpha and is used to treat rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis.

Soluble interleukin (IL) receptors (eg, those for IL-1, IL-2, IL-4, IL-5, and IL-6) are being developed for treatment of inflammatory and allergic disorders and cancer.

Recombinant cytokines

Colony-stimulating factors (CSF), such as erythropoietin, granulocyte CSF (G-CSF), and granulocyte-macrophage CSF (GM-CSF), are used in patients undergoing chemotherapy or transplantation for hematologic disorders and cancers and in patients with severe chronic neutropenia (see table Some Immunotherapeutic Agents in Clinical Use). Interferon-alpha (IFN-alpha) and IFN-gamma are used to treat cancer, immunodeficiency disorders, and viral infections; IFN-beta is used to treat relapsing multiple sclerosis. Many other cytokines are being studied.

Anakinra, used to treat rheumatoid arthritis, is a recombinant, slightly modified form of the naturally occurring IL-1R antagonist; this drug attaches to the IL-1 receptor and thus prevents binding of IL-1, but unlike IL-1, it does not activate the receptor.

Cells expressing cytokine receptors can be targeted by modified versions of the relevant cytokine (eg, denileukin diftitox, which is a fusion protein containing sequences from IL-2 and from diphtheria toxin). Denileukin is used in cutaneous T-cell lymphoma to target the toxin to cells expressing the CD25 component of the IL-2 receptor.

Small-molecule mimetics

Small linear peptides, cyclicized peptides, and small organic molecules are being developed as agonists or antagonists for various applications. Screening libraries of peptides and organic compounds can identify potential mimetics (eg, agonists for receptors for erythropoietin, thrombopoietin, and G-CSF).

Cellular therapies

Immune system cells are harvested (eg, by leukapheresis) and activated in vitro before they are returned to the patient. The aim is to amplify the normally inadequate natural immune response to cancer. Methods of activating immune cells include using cytokines to stimulate and increase numbers of antitumor cytotoxic T cells and using pulsed exposure to antigen-presenting cells such as dendritic cells with tumor antigens. Before being returned to the patient, T cells can be genetically engineered to express chimeric antigen receptors (CAR) or T cell receptors (TCR) capable of recognizing tumor antigens, an approach that has shown efficacy in patients with leukemia and lymphoma.

Drugs Mentioned In This Article

Drug Name Select Trade
Axicabtagene ciloleucel
PRADAXA
Brentuximab vedotin
Tisagenlecleucel
CYTOXAN (LYOPHILIZED)
Tildrakizumab
Obiltoxaximab
KEYTRUDA
OZURDEX
Sipuleucel-T
OTREXUP
TREANDA
BLINCYTO
Benralizumab
POMALYST
SOTRET
REVLIMID
Caplacizumab
LEUKERAN
Obinutuzumab
PRAXBIND
CARAC
ZINPLAVA
TECENTRIQ
ENTYVIO
NUCALA
Ocrelizumab
AVASTIN
ILARIS
TYSABRI
GEMZAR
DTIC-DOME
CAMPATH
CYRAMZA
No US brand name
VECTIBIX
ACTEMRA
RAXIBACUMAB
DARZALEX
HERCEPTIN
ELOXATIN
STELARA
THALOMID
ZEVALIN
SIMULECT
COSENTYX
UNITUXIN
PORTRAZZA
SYNAGIS
LUCENTIS
EMPLICITI
SOLIRIS
ALIMTA
ENBREL
REMICADE
HUMIRA
PERJETA
Durvalumab
Emicizumab
CAMPTOSAR
Lenvatinib
Guselkumab
Emapalumab
RAYOS
TAXOL
VELCADE
Siltuximab
PRALUENT
COLCRYS
REPATHA
XOLAIR
Reslizumab
Brodalumab
Ixekizumab
Ofatumumab
Ibalizumab
YERVOY
PLATINOL
REOPRO
ERBITUX
PROLIA
ORENCIA
OPDIVO
NEXAVAR
BENLYSTA
Burosumab
TAXOTERE
Sarilumab
HYCAMTIN
ALKERAN
Dupilumab
RITUXAN
SIMPONI
BAVENCIO
KINERET
Erenumab
Click here for Patient Education
NOTE: This is the Professional Version. CONSUMERS: Click here for the Consumer Version
Professionals also read

Also of Interest

Videos

View All
Overview of Type I Hypersensitivity
Video
Overview of Type I Hypersensitivity
Overview of Type II Hypersensitivity
Video
Overview of Type II Hypersensitivity

SOCIAL MEDIA

TOP