A number of immunologic interventions, both passive and active, can be directed against tumor cells. (See also Immunotherapeutics Immunotherapeutics 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 continuing to be developed. A number... read more .)
Passive Cellular Immunotherapy
In passive cellular immunotherapy, specific effector cells are directly infused and are not induced within the patient.
Lymphokine-activated killer (LAK) cells are produced from the patient’s T cells which are extracted from the tumor and grown in a cell culture system with the lymphokine interleukin-2 (IL-2). The LAK cells produced are then returned to the patient’s bloodstream. Animal studies have shown that LAK cells are more effective against cancer cells than are the original endogenous T cells, presumably because of their greater number. Clinical trials of LAK cells in humans are ongoing but this approach has not gained widespread use and is generally considered less effective than other cell therapies.
Tumor-infiltrating lymphocytes (TILs) may have greater tumoricidal activity than LAK cells. These cells are grown in culture in a manner similar to LAK cells. However, the progenitor cells consist of T cells isolated from resected tumor tissue. This process theoretically provides a line of T cells with greater tumor specificity than those obtained from the blood. Clinical studies have shown promise (1 Passive cellular immunotherapy references A number of immunologic interventions, both passive and active, can be directed against tumor cells. (See also Immunotherapeutics.) In passive cellular immunotherapy, specific effector cells... read more ).
Genetically modified T cells can express
T-cell receptors (TCR) recognize tumor-associated antigens Tumor Antigens Many tumor cells produce antigens, which may be released in the bloodstream or remain on the cell surface. Any molecule capable of being recognized by the immune system is considered an antigen... read more (TAAs) with high specificity to tumor cells. This approach has generally given way to CAR-T cell (see below)
Chimeric antigen receptors (CAR) recognize specific proteins on the surface of tumor cells. CAR T cells are used for patients with B-cell lymphomas Overview of Lymphomas Lymphomas are a heterogeneous group of tumors arising in the reticuloendothelial and lymphatic systems. The major types are Hodgkin lymphoma Non-Hodgkin lymphoma See table . Lymphomas were once... read more , acute lymphoblastic leukemia Acute Lymphoblastic Leukemia (ALL) Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer; it also strikes adults of all ages. Malignant transformation and uncontrolled proliferation of an abnormally differentiated... read more , and plasma cell myeloma Multiple Myeloma Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Common manifestations include lytic lesions in bones that cause... read more (2, 3 Passive cellular immunotherapy references A number of immunologic interventions, both passive and active, can be directed against tumor cells. (See also Immunotherapeutics.) In passive cellular immunotherapy, specific effector cells... read more ).
In contrast to TCR T cells, CAR T cells recognize only relatively large proteins on the surface of tumor cells. Therefore CAR T cells and TCR T cells may represent complementary approaches to cancer therapy.
Concomitant use of interferon enhances the expression of major histocompatibility complex (MHC) antigens and TAAs on tumor cells, thereby augmenting the killing of tumor cells by the infused effector cells.
Passive cellular immunotherapy references
1. Wang S, Sun J, Chen K, et al: Perspectives of tumor-infiltrating lymphocyte treatment in solid tumors. BMC Med 19, 140 (2021). https://doi.org/10.1186/s12916-021-02006-4
2. June CH, O'Connor RS, Kawalekar OU, et al: CAR T cell immunotherapy for human cancer. Science 359(6382):1361-1365, 2018. doi:10.1126/science.aar6711
3. Sadelain M, Brentjens R, Rivière I: The basic principles of chimeric antigen receptor design. Cancer Discov 3(4):388-398, 2013. doi:10.1158/2159-8290.CD-12-0548
Passive Humoral Immunotherapy
Administration of exogenous antibodies constitutes passive humoral immunotherapy. Although antilymphocyte serum was used in the treatment of chronic lymphocytic leukemia and in T-cell and B-cell lymphomas, resulting in temporary decreases in lymphocyte counts or lymph node size, newer humoral immunotherapeutic modalities have been developed.
T-cell engagers are bispecific antibodies that recruit cytotoxic T cells to kill tumor cells. The most frequently used engagers are antibodies targeting one tumor antigen and one molecule on T cells (mostly CD3). Antibodies targeting two tumor antigens and CD3 are being tested. T-cell engagers are effective in patients with B-cell precursor acute lymphoblastic leukemia Acute Lymphoblastic Leukemia (ALL) Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer; it also strikes adults of all ages. Malignant transformation and uncontrolled proliferation of an abnormally differentiated... read more and some other hematologic cancers. Efficacy in solid tumors is being studied (1 Passive humoral immunity references A number of immunologic interventions, both passive and active, can be directed against tumor cells. (See also Immunotherapeutics.) In passive cellular immunotherapy, specific effector cells... read more ).
Antibody-drug conjugates (ADC) may be used. Monoclonal antitumor antibodies may also be conjugated with different cell toxic drugs or with radioisotopes so that the antibodies deliver these toxic drugs selectively to the tumor cells. For example, a phase III trial of human epidermal growth factor receptor 2 (HER2; ERB2B)–targeting antibody conjugated with the topoisomerase I inhibitor demonstrated clinical benefits in patients with HER2-positive metastatic breast cancer (2). Other antibody-drug conjugates include gemtuzumab ozogamicin (acute myeloid leukemia), brentuximab vedotin (Hodgkin disease), inotuzumab ozogamicin (acute lymphoblastic leukemia, chronic lymphocytic leukemia), and polatuzumab vedotin (lymphoma) (3, 4 Passive humoral immunity references A number of immunologic interventions, both passive and active, can be directed against tumor cells. (See also Immunotherapeutics.) In passive cellular immunotherapy, specific effector cells... read more ).
Passive humoral immunity references
1. Baeuerle PA, Wesche H: T-cell-engaging antibodies for the treatment of solid tumors: challenges and opportunities. Curr Opin Oncol 34(5):552-558, 2022. doi:10.1097/CCO.0000000000000869
2. Cortes J, Kim SB, Chung WP, et al: Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. N Engl J Med 386(12):1143–1154, 2022. doi: 10.1056/NEJMoa2115022
3. Sliwkowski MX, Mellman I: Antibody therapeutics in cancer. Science 341(6151):1192-1198, 2013. doi:10.1126/science.1241145
4. Weiner LM, Murray JC, Shuptrine CW: Antibody-based immunotherapy of cancer. Cell 148(6):1081-1084, 2012. doi:10.1016/j.cell.2012.02.034
Active Specific Immunotherapy
Inducing cellular immunity Cellular Immunity The immune response to foreign antigens consists of Humoral mechanisms (eg, antibodies) Cellular mechanisms (See also Tumor Antigens.) Most humoral responses cannot prevent tumor growth. However... read more (involving cytotoxic T cells) in a host that failed to spontaneously develop an effective response generally involves methods to enhance presentation of tumor antigens to host effector cells. Cellular immunity can be induced to specific, very well-defined antigens. Several techniques can be used to stimulate a host response; these techniques may involve giving peptides, DNA, or tumor cells (from the host or another patient). Peptides and DNA can be delivered directly, transcutaneously to myeloid or dendritic cells using electroporation or injection with adjuvants, or indirectly using antigen-presenting cells (dendritic cells). These dendritic cells can also be genetically modified to secrete additional immune-response stimulants (eg, granulocyte-macrophage colony-stimulating factor [GM-CSF]).
Peptide-based vaccines use peptides from defined TAAs. An increasing number of TAAs have been identified as the targets of T cells in cancer patients and are being tested in clinical trials. Recent data indicate that responses are most potent if the TAAs are delivered using dendritic cells. These cells are obtained from the patient, loaded with the desired TAA, and then reintroduced intradermally; they stimulate endogenous T cells to respond to the TAA. The peptides also can be delivered by co-administration with immunogenic adjuvants (1 Active specific immunotherapy references A number of immunologic interventions, both passive and active, can be directed against tumor cells. (See also Immunotherapeutics.) In passive cellular immunotherapy, specific effector cells... read more ).
DNA vaccines use recombinant DNA that encodes a specific (defined) antigenic protein. The DNA is delivered directly via transcutaneous electroporation, incorporated into viruses that are injected directly into patients, or introduced into dendritic cells obtained from the patients, which are then injected back into them. The DNA expresses the target antigen, which triggers or enhances patients’ immune response. Clinical trials of DNA vaccines have shown promising results (2 Active specific immunotherapy references A number of immunologic interventions, both passive and active, can be directed against tumor cells. (See also Immunotherapeutics.) In passive cellular immunotherapy, specific effector cells... read more ).
Allogeneic tumor cells (cells taken from other patients) have been used in patients with acute lymphoblastic leukemia Acute Lymphoblastic Leukemia (ALL) Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer; it also strikes adults of all ages. Malignant transformation and uncontrolled proliferation of an abnormally differentiated... read more and acute myeloid leukemia Acute Myeloid Leukemia (AML) In acute myeloid leukemia (AML), malignant transformation and uncontrolled proliferation of an abnormally differentiated, long-lived myeloid progenitor cell results in high circulating numbers... read more . Remission is induced by intensive chemotherapy and radiation therapy. Then, irradiated allogeneic tumor cells that have been modified either genetically or chemically to increase their immunogenic potential are injected into the patient. Sometimes patients are also given bacille Calmette-Guérin (BCG) vaccine or other adjuvants (a therapeutic approach called nonspecific immunotherapy Nonspecific Immunotherapy A number of immunologic interventions, both passive and active, can be directed against tumor cells. (See also Immunotherapeutics.) In passive cellular immunotherapy, specific effector cells... read more ) to enhance the immune response against the tumor. Prolonged remissions or improved reinduction rates have been reported in some series but not in most (3 Active specific immunotherapy references A number of immunologic interventions, both passive and active, can be directed against tumor cells. (See also Immunotherapeutics.) In passive cellular immunotherapy, specific effector cells... read more ).
Messenger RNA (mRNA) vaccines were successfully used during the SARS-CoV-2 pandemic, which has sparked interest in developing them as an immunotherapeutic treatment for cancer (3 Active specific immunotherapy references A number of immunologic interventions, both passive and active, can be directed against tumor cells. (See also Immunotherapeutics.) In passive cellular immunotherapy, specific effector cells... read more ).
Active specific immunotherapy references
1. Stephens AJ, Burgess-Brown NA, Jiang S: Beyond Just Peptide Antigens: The Complex World of Peptide-Based Cancer Vaccines. Front Immunol 12:696791, 2021. Published 2021 Jun 30. doi:10.3389/fimmu.2021.696791
2. Lopes A, Vandermeulen G, Préat V: Cancer DNA vaccines: current preclinical and clinical developments and future perspectives. J Exp Clin Cancer Res 38(1):146, 2019. doi:10.1186/s13046-019-1154-7
3. Lin MJ, Svensson-Arvelund J, Lubitz GS, et al: Cancer vaccines: the next immunotherapy frontier. Nat Cancer 3 (8):911–926, 2022. doi: 10.1038/s43018-022-00418-6
Immunotherapy and Targeting Inhibitors of Immune Responses
Immune checkpoint blockers are antibodies that target molecules involved in natural inhibition of immune responses. These target molecules include the following:
Cytotoxic T lymphocyte-associated protein 4 (CTLA4)
Programmed cell death protein 1 (PD1) and programmed cell death ligands 1 (PD-L1) and 2 (PD-L2)
Others
Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) can downregulate the activation of CD4+ and CD8+ T cells that is triggered by antigen-presenting cells (APCs). The mechanism may be the higher affinity of CTL4 for CD80 and CD86 (costimulatory receptors) than the costimulatory receptor CD28 on APCs. CTLA-4 is upregulated by activation of T cell receptor and by cytokines such as interferon-gamma and interleukin-12. The CTLA-4 inhibitor ipilimumab prolongs survival in metastatic melanoma Melanoma Malignant melanoma arises from melanocytes in a pigmented area (eg, skin, mucous membranes, eyes, or central nervous system). Metastasis is correlated with depth of dermal invasion. With metastasis... read more and can be used as an alternative to interferon as adjuvant treatment in high-risk melanoma (1 Immunotherapy and immune inhibitors references A number of immunologic interventions, both passive and active, can be directed against tumor cells. (See also Immunotherapeutics.) In passive cellular immunotherapy, specific effector cells... read more ). Tremelimumab, another CTLA-4 inhibitor, is available for treatment of non-small cell lung cancer Classification Lung carcinoma is the leading cause of cancer-related death in men and women worldwide. About 85% of cases are related to cigarette smoking. Symptoms can include cough, chest discomfort or pain... read more (NSCLC) and other tumors (2 Immunotherapy and immune inhibitors references A number of immunologic interventions, both passive and active, can be directed against tumor cells. (See also Immunotherapeutics.) In passive cellular immunotherapy, specific effector cells... read more ).
PD-1 and PD ligand 1 and 2 inhibitors can counteract certain immune inhibitory effects triggered by the interaction of PD-1 and PD-L1 or PD-L2. PD-1 is expressed on T cells, B cells, natural killer (NK) cells, and some others (eg, monocytes, dendritic cells). It binds to PD-L1 (expressed on many tumor cells, hematopoietic cells, and some other cells) and PD-L2 (expressed mainly on hematopoietic cells). This binding inhibits tumor cell apoptosis and facilitates T-cell exhaustion and the conversion of T-cell cytotoxic and helper T cells to regulatory T cells. PD-1 and PD-L1/2 are upregulated by cytokines such as interleukin-12 and interferon-gamma in the tumor microenvironment and prevent T-cell activation and recognition of tumor cells.
Nivolumab and pembrolizumab are IgG4 PD-1 inhibitors that increase T-cell activation and infiltration of tumors and prolong survival in metastatic melanoma Melanoma Malignant melanoma arises from melanocytes in a pigmented area (eg, skin, mucous membranes, eyes, or central nervous system). Metastasis is correlated with depth of dermal invasion. With metastasis... read more , non-small cell lung cancer Lung Carcinoma Lung carcinoma is the leading cause of cancer-related death in men and women worldwide. About 85% of cases are related to cigarette smoking. Symptoms can include cough, chest discomfort or pain... read more , head and neck squamous cell cancer Oropharyngeal Squamous Cell Carcinoma Oropharyngeal cancer refers to cancer of the tonsil, base and posterior one third of the tongue, soft palate, and posterior and lateral pharyngeal walls. Squamous cell carcinoma comprises over... read more , kidney cancer Renal Cell Carcinoma Renal cell carcinoma (RCC) is the most common renal cancer. Symptoms can include hematuria, flank pain, a palpable mass, and fever of unknown origin (FUO). However, symptoms are often absent... read more , bladder cancer Bladder Cancer Bladder cancer is usually transitional cell (urothelial) carcinoma. Patients usually present with hematuria (most commonly) or irritative voiding symptoms such as frequency and/or urgency; later... read more , and Hodgkin lymphoma Hodgkin Lymphoma Hodgkin lymphoma is a localized or disseminated malignant proliferation of cells of the lymphoreticular system, primarily involving lymph node tissue, spleen, liver, and bone marrow. Symptoms... read more (3, 4 Immunotherapy and immune inhibitors references A number of immunologic interventions, both passive and active, can be directed against tumor cells. (See also Immunotherapeutics.) In passive cellular immunotherapy, specific effector cells... read more ).
Lymphocyte activator gene 3 (LAG-3) increases T cell regulator activity by interacting with MHC on tumor cells. Blockade of LAG3 with monoclonal antibody has demonstrated strong clinical benefit in patients with unresectable metastatic melanoma (5 Immunotherapy and immune inhibitors references A number of immunologic interventions, both passive and active, can be directed against tumor cells. (See also Immunotherapeutics.) In passive cellular immunotherapy, specific effector cells... read more ).
Others targeting inhibitors under study are generally in earlier stages of clinical development. These include, for example,
B- and T-cell lymphocyte attenuator (BTLA), which decreases production of cytokines and CD4 cell proliferation (6 Immunotherapy and immune inhibitors references A number of immunologic interventions, both passive and active, can be directed against tumor cells. (See also Immunotherapeutics.) In passive cellular immunotherapy, specific effector cells... read more )
T-cell immunoglobulin and mucin domain 3 (TIM-3), which kills helper Th1 cells (7 Immunotherapy and immune inhibitors references A number of immunologic interventions, both passive and active, can be directed against tumor cells. (See also Immunotherapeutics.) In passive cellular immunotherapy, specific effector cells... read more )
V-domain Ig suppressor of T-cell activation (VISTA), inhibition of which increases T-cell activity in tumors (8 Immunotherapy and immune inhibitors references A number of immunologic interventions, both passive and active, can be directed against tumor cells. (See also Immunotherapeutics.) In passive cellular immunotherapy, specific effector cells... read more )
Bispecific antibodies that target several of these molecules together have been developed and currently are being tested in clinical trials (9 Immunotherapy and immune inhibitors references A number of immunologic interventions, both passive and active, can be directed against tumor cells. (See also Immunotherapeutics.) In passive cellular immunotherapy, specific effector cells... read more ).
Combinations of immune checkpoint blockers (eg, blockade of CTLA-4 and PD-1 for metastatic melanoma or advanced renal cell cancer) are under investigation. Clinical trials have demonstrated substantial clinical benefits, but combinations of immune checkpoint inhibitors are associated with higher toxicity than monotherapy (2 Immunotherapy and immune inhibitors references A number of immunologic interventions, both passive and active, can be directed against tumor cells. (See also Immunotherapeutics.) In passive cellular immunotherapy, specific effector cells... read more ).
Combining immunotherapy and conventional chemotherapy is a novel approach to cancer treatment. It has shown some success (vs historic controls) in nonrandomized phase I and phase II clinical trials involving various cancers, types of vaccines, and chemotherapy. The combination of the checkpoint inhibitor pembrolizumab with chemotherapy is used as first-line treatment of metastatic squamous non–small cell lung cancer Lung Carcinoma Lung carcinoma is the leading cause of cancer-related death in men and women worldwide. About 85% of cases are related to cigarette smoking. Symptoms can include cough, chest discomfort or pain... read more (10 Immunotherapy and immune inhibitors references A number of immunologic interventions, both passive and active, can be directed against tumor cells. (See also Immunotherapeutics.) In passive cellular immunotherapy, specific effector cells... read more ). The combination of the check-point inhibitor atezolizumab with chemotherapy can be used to treat patients with triple-negative breast cancer Breast Cancer Breast cancers are most often epithelial tumors involving the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more (11 Immunotherapy and immune inhibitors references A number of immunologic interventions, both passive and active, can be directed against tumor cells. (See also Immunotherapeutics.) In passive cellular immunotherapy, specific effector cells... read more ). The PD-L1 check-point inhibitor durvalumab in combination with chemotherapy has demonstrated efficacy in patients with small cell lung cancer and after conventional chemotherapy in patients with non-small cell lung cancer (10 Immunotherapy and immune inhibitors references A number of immunologic interventions, both passive and active, can be directed against tumor cells. (See also Immunotherapeutics.) In passive cellular immunotherapy, specific effector cells... read more ).
Immunotherapy and immune inhibitors references
1. Hodi FS, O'Day SJ, McDermott DF, et al: Improved survival with ipilimumab in patients with metastatic melanoma [published correction appears in N Engl J Med 363(13):1290, 2010]. N Engl J Med 363(8):711-723, 2010. doi:10.1056/NEJMoa1003466
2. Johnson ML, Cho BC, Luft A, et al: Durvalumab with or without tremelimumab in combination with chemotherapy as first-line therapy for metastatic non-small-cell lung cancer: The Phase III POSEIDON Study. J Clin Oncol 41(6):1213-1227, 2023. doi:10.1200/JCO.22.00975
3. Tawbi HA, Schadendorf D, Lipson EJ, et al: Relatlimab and nivolumab versus nivolumab in untreated advanced melanoma. N Engl J Med 386(1):24–34, 2022. doi: 10.1056/NEJMoa2109970
4. Gandhi L, Rodriguez-Abreu D, Gadgeel S, et al: Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med 378(22):2078–2092, 2018. doi: 10.1056/NEJMoa1801005
5. Ruffo E, Wu RC, Bruno TC, et al: Lymphocyte-activation gene 3 (LAG3): The next immune checkpoint receptor. Semin Immunol 42:101305, 2019. doi:10.1016/j.smim.2019.101305
6. Ning Z, Liu K, Xiong H: Roles of BTLA in Immunity and Immune Disorders. Front Immunol 12:654960, 2021. doi:10.3389/fimmu.2021.654960
7. Acharya N, Sabatos-Peyton C, Anderson AC: Tim-3 finds its place in the cancer immunotherapy landscape. J Immunother Cancer. 2020;8(1):e000911. doi:10.1136/jitc-2020-000911
8. Hosseinkhani N, Derakhshani A, Shadbad MA, et al: The role of V-domain Ig suppressor of T cell activation (VISTA) in cancer therapy: Lessons learned and the road ahead. Front Immunol 12:676181, 2021. doi:10.3389/fimmu.2021.676181
9. Ordonez-Reyes C, Garcia-Robledo JE, Chamorro DF, et al: Bispecific antibodies in cancer immunotherapy: A novel response to an old question. Pharmaceutics 14(6):1243, 2022. doi:10.3390/pharmaceutics14061243
10. Paz-Ares L, Dvorkin M, Chen Y, et al: Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet 394(10212):1929–1939, 2019. doi: 10.1016/S0140-6736(19)32222-6
11. Schmid P, Adams S, Rugo HS, et al: Atezolizumab and Nab-Paclitaxel in advanced triple-negative breast cancer. N Engl J Med 379(22):2108–2121, 2018. doi: 10.1056/NEJMoa1809615
Nonspecific Immunotherapy
Interferons (IFN-alpha, IFN-beta, IFN-gamma) are glycoproteins that have antitumor and antiviral activity. Depending on dose, interferons may either enhance or decrease cellular immune function and humoral immune function Host Response to Tumors The immune response to foreign antigens consists of Humoral mechanisms (eg, antibodies) Cellular mechanisms (See also Tumor Antigens.) Most humoral responses cannot prevent tumor growth. However... read more . Interferons also inhibit cell division and certain synthetic processes in a variety of cells, including hematopoietic stem cells.
Interferons have antitumor activity in various cancers, including hairy cell leukemia, chronic myeloid leukemia Chronic Myeloid Leukemia (CML) Chronic myeloid leukemia (CML) occurs when a pluripotent stem cell undergoes malignant transformation and clonal myeloproliferation, leading to a striking overproduction of mature and immature... read more , myeloproliferative neoplasms Overview of Myeloproliferative Neoplasms Myeloproliferative neoplasms are clonal proliferations of bone marrow hematopoietic stem cells, which can manifest as an increased number of functionally normal platelets, red blood cells (RBCs)... read more , AIDS-associated Kaposi sarcoma Kaposi Sarcoma Kaposi sarcoma is a multicentric vascular tumor caused by herpesvirus type 8. It is categorized into 5 types: classic (sporadic), AIDS-associated (epidemic), non-epidemic, endemic (in Africa)... read more , non-Hodgkin lymphoma Non-Hodgkin Lymphomas Non-Hodgkin lymphomas are a heterogeneous group of disorders involving malignant, monoclonal proliferation of lymphoid cells in lymphoreticular sites, including lymph nodes, bone marrow, the... read more , multiple myeloma Multiple Myeloma Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Common manifestations include lytic lesions in bones that cause... read more , and ovarian cancer Ovarian, Fallopian Tube, and Peritoneal Cancer Ovarian cancer is often fatal because it is usually advanced when diagnosed. The most common histology—high-grade serous epithelial ovarian cancer—is considered as a single clinical entity along... read more (1 Nonspecific immunotherapy references A number of immunologic interventions, both passive and active, can be directed against tumor cells. (See also Immunotherapeutics.) In passive cellular immunotherapy, specific effector cells... read more ). However, interferons can have significant adverse effects, such as fever, malaise, leukopenia, alopecia, myalgia, cognitive and depressive effects, cardiac arrhythmias, and hypothyroidism.
Certain bacterial adjuvants (eg, bacille Calmette–Guérin [BCG] and derivatives, killed suspensions of Corynebacterium parvum) have tumoricidal properties. They have been used with or without added tumor antigen to treat a variety of cancers, usually along with intensive chemotherapy or radiation therapy. For example, direct injection of BCG into cancerous tissues has resulted in regression of melanoma Melanoma Malignant melanoma arises from melanocytes in a pigmented area (eg, skin, mucous membranes, eyes, or central nervous system). Metastasis is correlated with depth of dermal invasion. With metastasis... read more and prolongation of disease-free intervals in superficial bladder cancers Superficial cancers Bladder cancer is usually transitional cell (urothelial) carcinoma. Patients usually present with hematuria (most commonly) or irritative voiding symptoms such as frequency and/or urgency; later... read more and may help prolong drug-induced remission in acute myeloid leukemia Acute Myeloid Leukemia (AML) In acute myeloid leukemia (AML), malignant transformation and uncontrolled proliferation of an abnormally differentiated, long-lived myeloid progenitor cell results in high circulating numbers... read more , ovarian cancer Ovarian, Fallopian Tube, and Peritoneal Cancer Ovarian cancer is often fatal because it is usually advanced when diagnosed. The most common histology—high-grade serous epithelial ovarian cancer—is considered as a single clinical entity along... read more , and non-Hodgkin lymphoma Non-Hodgkin Lymphomas Non-Hodgkin lymphomas are a heterogeneous group of disorders involving malignant, monoclonal proliferation of lymphoid cells in lymphoreticular sites, including lymph nodes, bone marrow, the... read more (2 Nonspecific immunotherapy references A number of immunologic interventions, both passive and active, can be directed against tumor cells. (See also Immunotherapeutics.) In passive cellular immunotherapy, specific effector cells... read more ).
Nonspecific immunotherapy references
1. Arico E, Castiello L, Capone I, et al: Type I interferons and cancer: An evolving story demanding novel clinical applications. Cancers (Basel) 11(12):1943, 2019. doi:10.3390/cancers11121943
2. Gupta P, Chen C, Chaluvally-Raghavan P, Pradeep S: B Cells as an immune-regulatory signature in ovarian cancer. Cancers (Basel) 11(7):894, 2019. doi:10.3390/cancers11070894
Drugs Mentioned In This Article
Drug Name | Select Trade |
---|---|
gemtuzumab ozogamicin |
Mylotarg |
brentuximab vedotin |
ADCETRIS |
inotuzumab ozogamicin |
BESPONSA |
polatuzumab vedotin |
Polivy |
ipilimumab |
YERVOY |
tremelimumab |
IMJUDO |
nivolumab |
Opdivo |
pembrolizumab |
Keytruda |
atezolizumab |
Tecentriq |
durvalumab |
IMFINZI |