2009, Monday the 16th of March
Antigen Recognition by TCR Transduced Cells
Michael I. Nishimura, Ph.D.
Professor of Surgery and Microbiology & Immunology.
The Medical University of South Carolina, Charleston, SC 29425
It has been clearly demonstrated that tumor reactive T cells exist in the peripheral blood
and tumor lesions of cancer patients and that cancer vaccines can elevate the frequency of these
T cells in the blood of vaccinated patients. However, despite this increase in anti-tumor
reactivity in the blood of vaccinated patients, relatively few clinical responses are observed.
Given that most cancer vaccines target antigens which are nonmutated normal self proteins
expressed by the tumor, the failure to elicit clinically effective anti-tumor immunity may be the
result of immunologic tolerance. Therefore, until we can design better treatment strategies
capable of eliciting more effective anti-tumor immunity, the promise of immunotherapy for
cancer will go unfulfilled.
We have recently described using retroviral vectors containing T cell receptor (TCR)
genes to redirect the specificity of normal T cells. This methodology will not only allow us to
engineer any patients T cells to recognize the antigen of choice, we can select the TCR used
based on its affinity for antigen. Based on a detailed analysis of several TCRs, we have found
that it if the correct TCR is identified, it is possible to engineer potent anti-tumor effector cells,
major histocompatibility complex (MHC) class I restricted CD4+ T cells capable of providing T
cell help, and T cells capable of reacting with two distinct antigens. We have also devised novel
strategies to protect T cells from the host environment and to enhance their ability to recognize
antigen. We have also developed a novel preclinical animal model which will enable us to have
a better understanding of the biology of TCR transduced T cells and how they differ from normal
T cells. It is our belief that a better understanding of the biology of tumor reactive T cells
combined with the ability to provide any patient with a source of autologous T cells reactive with
one or more antigens expressed by their tumor will hopefully enable more cancer patients to
have the opportunity to benefit from immunotherapy.