Adoptive Cell Therapies
These therapies use patients’ own immune cells to mount a stronger attack on tumors by increasing the number and effectiveness of the body’s own immune cells thus resulting in a more powerful immune response against cancer.
Main types of adoptive cellular therapy:
- Chimeric antigen receptor (CAR) T-cell Therapy
T cells removed from patient’s blood are altered in the laboratory to add specific man-made receptors (CAR) to aid the T cells in identifying specific cancer cells. These altered T cells are then grown in the laboratory to increase in number and then returned to the patient’s body where they seek out and destroy the specific cancer. Prior to the modified T cells being returned to the patient, they must undergo chemotherapy or radiation to deplete the patient’s unaltered immune cells, as they might impede the modified T cells from effectively fight cancer cells.
This type of therapy has been shown to be successful in cancer cells where chemotherapy had failed in the past for some types of lymphomas (acute lymphoblastic leukemia and B- Cell lymphoma) and relapsed or hard to treat leukemia.
Example of FDA Approved Therapy:
Tisagenlecleucel (Kymriah, Novartis) is a CAR T-cell Therapy approved for certain types of lymphomas in children and adults. T cells that are taken from a patient are turned into Kymriah CAR T-cells that when returned to the patient are able to recognize antigens on B-cells and destroy them, including those containing cancer. Two severe side effects that are seen with CAR Ttherapy are cytokine release syndrome (CRS), an acute systemic inflammatory reaction characterized by fever and multiple organ dysfunction, and neurological toxicities.
- CAR natural killer (NK) cell Therapy
Tumor cells are known to have adapted mechanisms to avoid detection and inhibit the effectiveness of NK cells to identify and kill abnormal cells thereby impeding the immune response. Similar to CAR T therapy, NK cells are removed and engineered in the lab to better identify and kill specific cancer cells. However, the CAR-NK the cells are not required to be matched to a specific patient. While CAR T-cell therapies have already been approved by FDA, CAR NK-cell therapy is still novel immunotherapy only available through clinical trials.
- Tumor-infiltrating lymphocyte (TIL) Therapy
TILs are white blood cells that play an important role in anti-tumor immunity that express a variety of different antigens to regulate the immune response and suppress tumor growth. Research has shown that an increase in the expression of immune cells correlates with more favorable clinical outcomes in malignant cancers including colorectal, lung and breast cancer. Expression of TILs serve as prognostic biomarker in various cancers and thus provide a new avenue for targeted immunotherapy. Similar to CAR T-cell therapy, TIL therapy uses T cells isolated from a patient’s surgically removed tumor and expanded in the lab, significantly increasing the number of TILs, which are normally very low, prior to reintroducing them in the patient to enhance their function against the tumor.
- Endogenous T-cell (ETC) Therapy
Naturally expressed tumor reactive T cells are collected from a patient’s blood, filtered to select and enhance only those T cells that are able to recognize cancer cells and expanded in the lab prior to reintroducing them in the patient. While this was originally a very labor-intensive process, research has made significant head way in isolating and enhancing the expression of these T cells. Small initial clinical trials have shown complete and durable response in metastatic patients who have failed traditional chemotherapies and even immune checkpoint immunotherapies.
Oncolytic Virus Therapy
This type of therapy uses a non-pathogenic, genetically modified virus that aids the immune system in destroying cancer cells without harming healthy cells. The virus is directly injected into the tumor where it is able to enter the cancer cells and replicate uncontrollably until the cancer cell bursts and dies. Cancer cells release antigens upon apoptosis that trigger the immune system to mount a targeted response against all cancer cells with the same antigens.
Example of FDA Approved Therapy
Talimogene laherparepvec (T-VEC), an oncologic vaccine therapy approved to treat advanced melanoma skin cancer. It is derived from a genetically modified herpes virus and is injected directly into the melanoma cells where it continuously replicates causing the tumor cells to rupture and die. The exact mechanism in the immune system has not been fully elucidated, however it is believed that in addition to its local effects on the tumor cells it causes an immune response in the body against melanoma. This is thought to work by two different mechanisms.
When T-Vec is administered, it releases new viral particles that can trigger increased activity in the immune system in the location of the tumor, and lead to tumor cell death. These dying tumor cells release antigens which prime the immune system to fight these tumor cells at distant sites or during reoccurrence.
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