T Cell-Based Cancer Therapy

T cell is another arm of immune system that protects human body from pathogens (antigens). For treatment and prevention of tumors, eliciting a strong cellular or T cell immune response is critical. The cellular response is comprised of activated cytotoxic T lymphocyte (CTL) and helper T lymphocyte (HTL) that are directed toward multiple discrete and specific antigen fragments, known as antigen-specific epitopes. The activated T cells have special molecules similar to antibodies on the surface. These special molecules allow T cells to recognize, react to, and destroy cancer cells. Compare to the antibody technology, limited advancement is achieved in the area of T cell technology. So far, there isn't any marketed anti-cancer product derived from T cell-based technology. However, significant progresses are being made in this field.

One of the most important advancement is the identification of numerous immunogenic tumor antigens that are recognized by autologous T cells. The T cell-defined tumor antigens are potential tumor-rejection antigens that can be targeted by augmenting the antigen-specific immune response in one of two ways: adoptive T-cell therapy or vaccine therapy.

Adoptive T-cell therapy involves the ex vivo isolation and expansion of antigen-specific T-cell clones. These can be infused into patients to augment their immune response. To achieve their goal, the primed CTLs must expand to sufficient numbers, migrate to tumour sites, mature into effector cells and perform their cytolytic functions. Tumors, in turn, exploit several mechanisms to elude or derail immunity. These include the ability to inactivate T cells through mechanisms such as anergy, apoptosis and suppression. Another challenge for cancer T cell immunity is to overcome the tumor's abilities to escape from the immune response.

The ability to genetically engineer primary T cells creates new prospects for the T cell-based cancer therapy. The transduction of T cells with genes that encode antigen receptors enables the recognition of antigens that are either poorly immunogenic or ignored by the immune system. Another important impetus for genetically modifying T cells is to enhance their antitumoral activities. This might be accomplished on different levels, such as by increasing T-cell expansion, offsetting anergizing or pro-apoptotic signals, expanding the range of tumoricidal functions and protecting T cells against the suppressive effects of the tumor microenvironment.

One example of T cell-based therapy is Dendreon's proprietary Antigen Delivery Cassette technology and dendritic/cancer cell fusion technology. The vaccine is created by fusing the patient's own tumor cells/proteins with powerful, immune-stimulating dendritic cells. The fusion product is then injected back into the patient with the goal of sparking a specific immune response (T-cells) against the cancer. Lapuleucel-T and Sipuleucel-T are generated by this technology. Lapuleucel-T targets HER2/neu positive cancers. HER2/neu is a growth factor receptor, and its overexpression has been associated with a number of cancers including breast, ovarian, colon and lung cancers. The HER2/neu protein is delivered to a patient's antigen presenting cells (APCs), dendritic cells. These APCs activate other cells (including T-cells) of the immune system to seek out and destroy HER2/neu-containing cancer cells. Sipuleucel-T targets the prostate cancer antigen, prostatic acid phosphatase (PAP), which is found in approximately 95% of prostate cancers.

INGN 225 is a personalized therapeutic vaccine consisting of a cancer patient's dendritic cells treated with an adenovector carrying the human p53 gene (Ad-p53). When these modified dendritic cells are returned to the patient's body, they activate the patient's T-cells to seek out and destroy cancer cells.

MDX-1379 is made up of two peptides that are pieces of a bigger melanoma protein (gp100). These peptides bind to HLA-A2 which is then recognized by T cells.