cancer immunotherapy strategies

Last edited 12/2019 and last reviewed 03/2022

Cancer immunotherapy strategies

• as part of its normal function, the immune system detects and destroys abnormal cells
  • most likely prevents or curbs the growth of many cancers
    • immune cells are sometimes found in and around tumours
      • these cells, tumour-infiltrating lymphocytes or TILs, are a sign that the immune system is responding to the tumour
      • tumours containing TILs often do have an improved prognosis compared to which tumours do not contain them.

Even though the immune system can prevent or slow cancer growth, cancer cells have ways to avoid destruction by the immune system:

• cancer cells may
  • have genetic changes that make them less visible to the immune system
  • have proteins on their surface that turn off immune cells
  • change the normal cells around the tumour so they interfere with how the immune system responds to the cancer cells

Immunotherapy enables the immune system to better act against cancer - in effect, immunotherapy enhances a person's own immune system to combat cancer - in contrast to chemotherapy agents which suppress a person's immune system as well as suppressing growth of the cancer.

Several types of immunotherapy are used to treat cancer

• includes passive or active immunotherapy
  • passive immunotherapy is administration of agents such as monoclonal antibodies, lymphocytes or cytokines that enhance existing anti-tumour response
  • active immunotherapy attempts to stimulate self-immune system to attack tumour cells via vaccination, non-specific immunomodulation, or targeting specific antigen receptors

These include:

Immune checkpoint inhibitors, which are drugs that block immune checkpoints. These checkpoints are a normal part of the immune system and keep immune responses from being too strong. By blocking them, these drugs allow immune cells to respond more strongly to cancer.

• a class of drugs aimed to increase immune response against cancer cells
• immune system consists of various checkpoint pathways focusing on T-cell activation that play an important role in modulating anti-tumour immunity
• molecules that play a crucial role in checkpoint regulation include the T-cell surface molecules CTLA-4, PD-1, T-cell immunoglobulin and mucin domain containing protein 3 (Tim-3), and lymphocyte activation gene-3 (LAG-3)
  • tumour expressions of these markers will results in hyporesponsiveness or even exhaustion of the immune system - targets for removing the inhibition and enable cytotoxic T cells to attack cancer cell for destruction

T-cell transfer therapy, which is a treatment that boosts the natural ability of your T cells to fight cancer.

• adoptive cell transfer (ACT) of tumour-associated antigen-specific T cells is a form of immunotherapy for hematologic malignancies as well as solid cancers
• two major sources of T cells for ACT are the tumour itself and the peripheral blood of the cancer patient
• T-cell transfer therapy may also be called adoptive cell therapy, adoptive immunotherapy, or immune cell therapy.

Monoclonal antibodies (MABs), which are immune system proteins created in the lab that are designed to bind to specific targets on cancer cells.

• antibodies are modified proteins aimed at to target a specific part of deregulated signals transduction pathways in cancer or interfere with immunological processes
• MABs recognise and attach to specific proteins on the surface of cancer cells
  • MAB therapies mimic natural antibodies, but are made in a laboratory
  • monoclonal means all one type. So each MAB therapy is a lot of copies of one type of antibody
  • naked mAbs are the most common type of mAbs for treating cancer, and it can work via boosting the immune response against cancer cells and acting as a marker for the immune system's destroying them
    • alemtuzumab is an example of naked mAb which can bind to the CD52 antigen on lymphocytes attacking them which is used to treat chronic lymphocytic leukemia (CLL)
  • conjugated mAbs are those mAbs joining to a chemotherapy agent or a radioactive particle taking one of these substances directly to the cancer cells
    • targets CD30 antigen found on lymphocytes, attaching to a chemotherapy drug and thus treating Hodgkin lymphoma and anaplastic large cell lymphoma
  • bispecific mAbs are made up of parts of 2 different mAbs, like blinatumomab binding to both CD3 and CD19 used to treat acute lymphocytic leukemia (ALL)

Monoclonal antibodies may also be called therapeutic antibodies.

Treatment vaccines, which work against cancer by boosting your immune system's response to cancer cells. Treatment vaccines are different from the ones that help prevent disease:

• cancer vaccines are the response modifiers working by stimulating or restoring the ability of immune system to fight cancer
  • consists of preventive vaccines and therapeutic vaccines
  • goal of preventive vaccine is preventing cancer from developing.
  • based on antigens carried by infectious agents and easy for the immune system to recognize as foreign invaders

Immune system modulators, which enhance the body's immune response against cancer. Some of these agents affect specific parts of the immune system, whereas others affect the immune system in a more general way

• types of immune-modulating agents include:
  • cytokines, which are proteins made by white blood cells
    • roles in body's normal immune responses and in the immune system's ability to respond to cancer
    • cytokines that are sometimes used to treat cancer include
      • Interferons (INFs) - for example INF-alfa, can enhance your immune response to cancer cells by causing certain white blood cells, such as natural killer cells and dendritic cells, to become active. INF-alfa may also slow the growth of cancer cells or promote their death
      • Interleukins (ILs) - IL-2, which is also called T-cell growth factor - boosts the number of white blood cells in the body, including killer T cells and natural killer cells
    • BCG in bladder cancer - - when inserted directly into the bladder with a catheter, BCG causes an immune response against cancer cells
    • immunomodulatory drugs (also called biological response modifiers) stimulate the immune system
      • include: Thalidomide, Lenalidomide, Pomalidomide and Imiquimod
      • thalidomide, lenaliodomide, and pomalidomide cause cells to release IL-2
        • also inhibit tumours from forming new blood vessels - these three drugs may also be called angiogenesis inhibitors.

Reference:

• Brooks M, Olsson-Brown A. Summary on Immunotherapy for Palliative Care Teams (Accessed 1/12/19)
• Haanan J et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, Annals of Oncology 2017; 28 (Supplement 4)
• Zhang H, Jibei C. Current status and future directions of cancer immunotherapy. Journal of Cancer 2018; 9(10): 1773-1781.