Immunotherapy

Is Vaccination against Cancer the Answer?

Initially considered a part of chemotherapy, cancer immunotherapy is evolving into its own class of treatments. The basic purpose is to stimulate a person’s immune system to build up its defenses against cancer to prevent its spread and eventually eliminate cancerous cells. The process, which most of us have experienced in childhood, is vaccination with a laboratory-manufactured antigen (vaccine) which stimulates the creation of disease fighting antibodies. Cancer vaccines can be made from the patient’s own tumor antigens or cells (autologous vaccine) or from someone else’s (allogeneic vaccine).

The elements of the immune system are your body’s soldiers. Dendritic cells act as scouts seeking out infections or diseases. When found the scouts capture data about the foreign cells and instruct the killer T-cells to attack and destroy it. The problem is that our “armies” are under-staffed, so the number of killer T-cells programmed to attack the tumor are insufficient to overwhelm it, unless the immune system can be stimulated to attack more aggressively (co-stimulation). The objective of immunotherapy is to get the immune system to direct a greater percentage of its killer T-cell army against the patient’s tumor to increase the probability of victory. Hoooah!

All T cells derive from haematopoietic stem cells in the bone marrow.

There are several types of T cells, each with its own function:

(1) Cytotoxic T cells (Tc), also know as C8+ T cells, destroy viral infections and tumor cells and are instrumental in transplant rejections.

(2) Helper T cells (Th) when activated divide rapidly and secrete small proteins (cytokines) that help the immune response. These cells are also the target of HIV infection.

(3) Regulatory T cells (Treg) act to shut down T cell mediated immunity toward the end of an immune reaction to prevent a body-damaging autoimmune response. Treg cells can be distinguished from other T cells by the presence of a FOCP3 intercellular molecule. Mutations of FOXP3 can prevent Treg development leading to a fatal autoimmune response.

(4)Natural Killer T cells (NKT) are lymphocytes that link the adaptive immune system with the innate immune system. Once activated these cells can perform the functions of Cytotoxic and Helper T cells, the release of cell killing molecules and cytokine production.

T cell Development and Activation

All T cells derive from haematopoietic stem cells in the bone marrow. The activation process begins with the release of hematopoietic (blood forming)progenitor stem cells populate the thymus and expand by cell division to create immature thymocytes - a lymphocyte that develops in the thymus and is the precursor of a T cell.

The thymocytes pass through a multi-stage process and emerge from the thymus into the surround tissue as immunocompetant T cells. Only 2% of thymocytes complete the process. The surviving cells are then activated through interaction with certain pre-existing antigen complexes or by molecular co-stimulation with antigen-presenting cells (APCs).

Certain cancer vaccines have added ingredients (adjuvents) that increases the antigenic response. Adjuvents include things like cytokines, proteins, bacteria, viruses, and chemicals. There have been promising results from studies in which vaccine has been used before or after treatment by other Cytotoxic treatments, as well as, vaccine alone.

Some vaccines, such as Ipilimumab, using monoclonal antibodies, identifiable by drug names ending in –mab, have shown promising results for some cancers, including melanoma.

The first vaccine approved in 1981 for cancer prevention protects against HBV infection (hepatitis B). Most children are vaccinated against HBV infection shortly after birth. In 2006 and 2008, Gardasil was approved for prevention of cervical cancer caused by human papillomavirus (HPV) types 6, 11, 16, and 18. Types 6 and 11 cause about 90% of genital warts; 16 and 18 cause about 70% of cervical cancers.

At this point, there are no other vaccines approved as mainline cancer treatments. There are many vaccines being tested in clinical trials, forty-five listed for melanoma. Here’s a typical example:

Vaccine Therapy in Treating Patients With Recurrent Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery

Alternate Title: Pilot Study of a Peptide Vaccine Comprising MART-1:27-35 Peptide, gp100:209-217 (210M) Peptide, and Tyrosinase Peptide With Sargramostim (GM-CSF) and CpG 7909 Emulsified in Incomplete Freund's Adjuvant in Patients With Unresectable Recurrent Stage III or IV Melanoma.

Purpose: Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Giving vaccine therapy together with GM-CSF, CpG 7909, and incomplete Freund's adjuvant may make a stronger immune response and kill more tumor cells. This clinical trial is studying the side effects and how well vaccine therapy works in treating patients with recurrent stage III or stage IV melanoma that cannot be removed by surgery.

More information about vaccines and clinical trials can be found at cancer.gov.

So, forget all the mumbo jumbo, forget about looking for a quick fix, and support stem cell research. When the breakthrough in cancer treatment comes it will be huge and vaccines will be an important element.