Immunology Graduate Group
Mark L. Tykocinski, M.D.
Simon Flexner Professor and Chair
Department of Pathology and Laboratory Medicine
Address: 6 Gates Pavilion
3400 Spruce Street Philadelphia, PA 19104
Office Phone: 215-662-6880
Fax: 215-662-4063
Research Summary
Our laboratory group has three funded research programs that deal in common with the design and functional analysis of proteins with immunotherapeutic potential. Two of these programs are geared towards proteins that can be used for engineering immunotherapeutic antigen-presenting cells ("APC").
Our unique angle stems from concentrating upon protein transfer (instead of gene transfer) as an APC engineering tool. To this end, we have been innovating protein transfer modalities, including the use of various genetically-engineered variants (including glycosyl-phosphatidylinositol ("GPI")-modified, Fc-modified, as well as other novel fusion protein variants) of immune cell surface proteins, such as costimulators and MHC proteins, as "protein paints" to confer new trans signaling functions to APC cell surfaces. We are devising novel cellular immunotherapies based upon such protein transfer that either enhance APC function (and are applicable to cellular cancer vaccine production) or reduce APC function (and are applicable to "artificial veto cell", i.e., deletional APC, production).
A third program in the lab deals with a unique immunoregulatory protein found at high levels in the amniotic fluid and serum of pregnancy and called placental protein 14 ("PP14"). Having chanced upon PP14 mRNA during a differential cDNA cloning project, we have been dissecting PP14 protein's immunoregulatory properties. Our recent data have established that PP14 inhibits T cells directly, and it does so in a unique way by elevating the T cell receptor activation threshold. This mechanism of action may account for some of the immunological findings in pregnancy, including, we hypothesize, the shift to Th2 cytokines and the temporary amelioration of cell-mediated autoimmune diseases during pregnancy. We are configuring protein and gene therapies for autoimmunity and alloimmunity around PP14.
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