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A popular topic in cancer research is the design of vaccines for prevention of the disease.  Just like with other vaccines, the goal of this venture is to train the body to recognize and combat cancer cells.  Because the human immune system is a vast network of chemical and cellular interactions, approaches targeting every aspect of the system are being applied.  Below is a list of the types of strategies utilized, and a small portion of the ongoing clinical studies for each approach. 

1) Innate Immunity Strategies

In the case of external pathogens, before they infect the human body, viruses, bacteria, and other microorganisms must first pass through the obstacles that represent the body’s first-response defense system.  These areas (the skin, mucous linings, and the blood-brain barrier) are stocked with white blood cells, such as Natural Killer (NK) cells, neutrophils, and macrophages.  The binding of certain molecules to the Toll-like receptors (TLRs) on these cells’ surfaces activates these white blood cells for highly efficient immune defense.  One approach to a cancer vaccine is represented by the design of molecules that can act precisely as TLR-activators.  In cancer, the pathogen is not external, but is the patient’s own cancer cell.  Although there is no actual invasion through the external barriers as there is with external microbes, the activation of TLRs on white blood cells can nevertheless contribute to effective clearance of the malignant cells.

  • A clinical trial of an adjuvant vaccine for high risk melanoma is ongoing at the Ludwig Institute for Cancer Research in New York.
  • Research at the Radboud University in Netherlands is observing the safety and dosage of TLR-based vaccines.

2) Adaptive Immunity Strategies

The T and B-lymphocytes represent white blood cells that bestow immunologic memory, a common basis for vaccination in general.  The process by which T-cells become activated as ‘defenders’ of the organism involves the bound formation of a triplet complex: T-cell + Antigen Presenting Cell (APC) + antigen degraded to a shorter segment.  One area of research into the cancer vaccine focuses on the synthesis of short segments of antigens that stimulate the immune response via T-cells in this way. 

  • Peptide vaccine + chemotherapy after surgery for stage III or stage IV is being tested for ovarian cancer, primary peritoneal cancer, and fallopian tube cancer at the University of Virginia.
  • A trial at the National Institutes of Health Clinical Center (CC) in Maryland is recruiting patients with lung, esophageal and thymic cancers, and mesotheliomas.  Antigens from these cancers are to be tested, along with chemotherapy drugs that may enhance the vaccine. 

3) Antibody Strategies

Antibodies are parts of B-cells that are cleaved off into the blood stream in response to an infection with a pathogen.  While it is still uncertain whether antibodies contribute much to an effective immune response in cancer, they are certainly considered useful for the diagnosis and prognosis of the disease.  Most of the spotlight for cancer vaccine research centers around T-cell activity.  However, some evidence for increased immunity with the formulation of antibodies in conjunction with T-cell therapies, has been reported.

  • A clinical trial on antibody production in patients with glioblastoma (brain tumor) following a tumor vaccine intervention is recruiting patients at the Dartmouth-Hitchcock Medical Center in New Hampshire.
  • Clinical research on antibodies in addition to a tumor vaccine for ovarian, epithelial, fallopian tube, and peritoneal cancer has been completed at Memorial Sloan-Kettering Cancer Center in New York.
  • Another study on an antibody vaccine in colorectal cancer has been completed by the Alliance for Clinical Trials in Oncology.

4) Cytokine Strategies

Cytokines are various molecules that either promote or oppose the activity of tumor cells.  Some cytokines aid tumors by inhibiting T-cells.  Techniques for targeting these cytokines to prevent T-cell inhibition constitute one of the approaches to the cancer vaccine.  Other cytokines, such as Tumor Necrosis Factor (TNF), act as anti-cancer agents.

  • At the National Institutes for Health Clinical Center in Maryland, TNF is being analyzed in patients undergoing surgery for primary and metastatic cancer.
  • Granulocyte-macrophage colony-stimulating factor (GMCSF) is being tested in a vaccine trial by Gradalis, Inc.

5) Whole Cell Strategies

In certain cases, whole tumor cells are included in the vaccine to induce an immune response.  Dendritic cells and APCs can be fused to the tumor cells to represent one part of the complex which, when finally bound to the T-cells, triggers the adaptive immune response. 

  • Two clinical trials at the Beth Israel Deaconess Medical Center in Boston are looking at a Dendritic + Tumor cell fusion vaccine, supplemented with Interleukin-12 and Imiquimod.
  • Clinical trials of two vaccines made by genetic modification of patients’ own breast cancer cells have been initiated at the Dana-Farber Cancer Institute in Boston.
  • Two clinical trials for two tumor cell vaccines in formulation with an experimental and anti-inflammatory drug are currently recruiting participants at the National Cancer Institute in Maryland.

 

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Written by Julia Yusupova

 

 

 

 

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