Dr. Touloukian’s lab has concentrated its efforts on the development of a model in which the host immune system is permanently reconfigured with a high frequency T cell population capable of recognizing a key antigenic component found on the surface of melanoma. In a recently published report, his lab has used a high expression lentiviral system to introduce the T cell receptor (TCR) genes from a tumor reactive HLA-DR4-restricted CD4+ T cell clone specific for the melanocyte differentiation antigen TRP-1 in hematopoietic stem cells (HSCs). Studies demonstrated high efficiency TCR gene transfer in long-term transplants, the induction of spontaneous autoimmune vitiligo, and the induction of a TCR-specific TH1 polarized memory effector (TEM) CD4+ T cell population. Most importantly, studies revealed the rejection of subcutaneous melanoma without the aid of vaccination, myelodepletion, or cytokine administration. This work was supported by an R01 grant, and his lab is currently in the implementation stages of a new clinical trial for patient’s metastatic melanoma that is being supported by the V Foundation. In parallel with this work, Dr. Touloukian’s lab is also addressing basic mechanisms of immune engraftment, thymic selection, promiscuous antigen expression, and how tumor responses can be more effectively elicited and sustained over time. My Laboratory research is directed specifically at one of those basic mechanistic barriers. The immune systemic has evolved to not only protect us from the dangers of the outside world (such as viruses, bacteria, and other pathogens), but also from ourselves in the form of self-attack. Over the past 20 to 30 years, patients with advanced metastatic cancer have been enrolled in a series of developing clinical trials that have attempted to exploit the specific and potent effects of the body’s own immune system. Current Projects:
- Transplantation of gene modified hematopoietic stem cells in the treatment of metastatic melanoma in both animal models and in patients
- Role of CD4 T cells in an anti-tumor immunity
- Identification of unique human lymphocyte progenitor populations from bone marrow, cord blood, peripheral blood and thymus
- Use of lentiviral vectors to deliver antigen specific T cell receptor genes (TCRs) to stem cell and progenitor cell populations
- Identification of novel epithelial subpopulations within the thymus and peripheral lymphoid organs that promiscuously express tissue specific antigens and to study their secondary effects on immune tolerance
- Identification of mechanisms involved in driving promiscuous expression of tissue specific antigens
