Immune therapy is the newest systemic cancer therapy (see also Immunotherapy of Cancer Immunotherapy of Cancer 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 ). Immune therapy is divided into two forms:

Active: Treatment is mediated by active immunity and aims to provoke or amplify a patient's anticancer immune response

Adoptive; Treatment is mediated by passive immunity and involves giving anticancer antibodies or cells

Active immune therapy can involve vaccines Vaccines Systemic cancer therapy includes chemotherapy (ie, conventional or cytotoxic chemotherapy), hormone therapy, targeted therapy, and immune therapy (see also Overview of Cancer Therapy). The number... read more , modified T-cells Modified T cells Systemic cancer therapy includes chemotherapy (ie, conventional or cytotoxic chemotherapy), hormone therapy, targeted therapy, and immune therapy (see also Overview of Cancer Therapy). The number... read more from the patient (eg chimeric antigen receptor (CAR)-T-cells), or certain types of monoclonal antibody Monoclonal antibodies Systemic cancer therapy includes chemotherapy (ie, conventional or cytotoxic chemotherapy), hormone therapy, targeted therapy, and immune therapy (see also Overview of Cancer Therapy). The number... read more that activate the patient's immune system against the cancer (eg, checkpoint inhibitors). Another example of active immune therapy is instilling bacille Calmette–Guérin (BCG) in the bladder of patients with bladder cancer.

Adoptive immune therapy often involves giving monoclonal antibodies Monoclonal antibodies Systemic cancer therapy includes chemotherapy (ie, conventional or cytotoxic chemotherapy), hormone therapy, targeted therapy, and immune therapy (see also Overview of Cancer Therapy). The number... read more produced in the laboratory or giving modified T cells Modified T cells Systemic cancer therapy includes chemotherapy (ie, conventional or cytotoxic chemotherapy), hormone therapy, targeted therapy, and immune therapy (see also Overview of Cancer Therapy). The number... read more or natural-killer (NK) cells from a healthy person to someone with cancer. Sometimes these cells are genetically modified by inserting an anticancer chimeric antigen receptor (CAR). Other forms of adoptive immune therapy include lymphokines and cytokines such as interferons and interleukins. These forms are less widely used in cancer therapy.

Vaccines designed to trigger or enhance immune system response to cancer cells have been extensively studied and have typically provided little benefit. However, sipuleucel-T, an autologous dendritic cell–derived vaccine is available for prostate cancer.

More important are vaccines designed to prevent virus-related cancer. Examples include vaccines to human papillomavirus Human Papillomavirus (HPV) Vaccine Human papillomavirus (HPV) infection is the most common sexually transmitted disease. HPV can cause skin warts, genital warts, or certain cancers, depending on the type of HPV. Vaccines are... read more (HPV), which can prevent cervical and anal cancers (and possibly and head and neck and tonsil cancers) and vaccines to hepatitis B virus Hepatitis B (HepB) Vaccine The hepatitis B vaccine is 80 to 100% effective in preventing infection or clinical hepatitis B in people who complete the vaccine series. For more information, see Hepatitis B Advisory Committee... read more (HBV), which can prevent liver cancer.

In this technique, T cells are removed from the blood of a patient with cancer, modified genetically to recognize a cancer-related antigen, and returned to the patient. The most common example of this strategy is termed chimeric antigen receptor (CAR)-T-cells. CAR-T-cells are an effective therapy in patients with acute lymphoblastic leukemia, B-cell lymphomas, and multiple myeloma. Recently, two CAR-T-cell therapies, tisagenlecleucel for young patients with advanced acute lymphoblastic leukemia and axicabtagene ciloleucel for advanced lymphomas, became available. Other CAR-T-cell drugs include brexucabtagene autoleucel, idecabtagene vicleucel, and lisocabtagene maraleucel. They are not yet proved effective in solid cancers.

Related techniques involve growing the extracted T cells in a culture and activating them by exposure to lymphokine interleukin-2 (IL-2). Alternatively, T cells may be extracted from the patient's tumor, cultured to create a larger amount and then reinfused.

Monoclonal antibodies are widely used to treat some cancers. Monoclonal antibodies can be directed against antigens that are cancer-specific or over-expressed on cancer cells. They can also be directed toward lineage-specific antigens also present on normal cells. Some monoclonal antibodies are given directly; others are linked to a radionuclide or toxin. These linked antibodies are referred to as antibody-drug conjugates (ADCs). Some antibodies are bi-specific, with one receptor directed to a cancer-related antigen and another to an antigen on T cells. The goal is to bring T cells to the cancer to eradicate it.

Trastuzumab, an antibody directed against a protein called ERBB2, is active in breast cancers that express this antigen. Antibodies to CD19 and CD20 on normal B cells are used to treat lymphomas (rituximab), anti-CD30 antibodies are used to treat Hodgkin lymphoma (brentuximab vedotin), and anti-CD33 antibodies are used to treat acute myeloid leukemia (gemtuzumab ozogamicin).

Several monoclonal antibodies activate dormant or blocked anti-cancer immunity (active immune therapy) by binding immune checkpoint inhibitors, molecules involved in natural inhibition of immune responses. Blocking this inhibition releases a patient's immune response suppressed by the tumor. Target molecules include 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). CTLA4 inhibitors include ipilimumab and tremelimumab. PD1 blockers include cemiplimab, dostarlimab, nivolumab, and pembrolizumab, and PD-1L blockers include atezolizumab, avelumab, and durvalumab. These drugs are being widely used to treat diverse solid cancers, alone or combined with chemotherapy; they are not effective against blood and bone marrow cancers.

Most recently, anticancer monoclonal antibodies that target 2 or 3 antigens have been developed. These monoclonal antibodies typically target cancer-related antigens and T-cell antigens to enhance T-cell killing of cancer cells. Blinatumomab, which targets CD19 on acute lymphoblastic leukemia cells and CD3 on T cells, is an example.