vaccines-gynecologic-oncology-2018-posters

Page 69

Journal of Clinical Immunology and Allergy

ISSN: 2471-304X

E u r o p e a n C o n g r e s s o n

Vaccines & Vaccination

and Gynecologic Oncology

Vaccines & Vaccination and Gynecologic Oncology 2018

O c t o b e r 2 6 - 2 7 , 2 0 1 8

B u d a p e s t , H u n g a r y

onor-specific anti-tumor T cells have been generated by engineering human primary T cells with tumor-associated antigen-specific

T cell receptor (TCR) or chimeric antigen receptor (CAR). Both of these approaches have produced remarkable clinical outcomes,

however, success rate of these approaches require significant improvement. In this context, availability of methods to generate T cells

with customized effector function profiles would be useful. Although activation induced cell death (AICD) and program cell death (PCD)

are essential immune homeostasis mechanisms, characterization of the mechanism of epitope-specific AICD in human primary T

cells could help generate anti-tumor T cells that would sustain longer in the physiology and produce superior clinical outcomes. Utiliz-

ing human melanoma-associated antigen-specific anti-tumor T cell-derived MHC class I restricted transgenic TCRs, we have recently

generated CD4

and CD8

multifunctional anti-tumor T cells. We have found that human melanoma-associated antigen-specific MHC

class I restricted transgenic T cell receptor (TCR) engineered (TCR engg) CD4

and CD8

T cells exhibit differential susceptibility to epi-

tope-specific AICD, such that while TCR engg CD8

T cells undergo AICD even upon encountering their target epitope for the very first

time, TCR engg CD4

T cells become susceptible to AICD following one encounter with the target epitope. We have also characterized

the mechanism of AICD in TCR engg human primary T cells and shown that JNK, BCL-family proteins, and p53-mediated non-tran-

scription dependent pathway plays an essential roles in it. We will discuss different approaches being pursued towards generating

long-lasting anti-tumor T cells with customized anti-tumor effector function profile that could help improve the efficacy of current

immunotherapy approaches.

Engineering anti-tumor immune response with

customized functional profile

Arvind Chhabra

Amity University Gurgaon, India

Journal of Clinical Immunology and Allergy, Volume: 4

DOI: 10.21767/2471-304X-C2-006

Euro Vaccines 2018