Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q04609 (prostate-specific membrane antigen)
 1,287 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Artificial receptors provide a promising approach to target T lymphocytes to tumor antigens. However, the receptors described thus far produce either an activation or a co-stimulatory signal alone, thus limiting the spectrum of functions accomplished by the genetically modified cells. Here we show that human primary T lymphocytes expressing fusion receptors directed to prostate-specific membrane antigen (PSMA) and containing combined T-cell receptor-zeta (TCRzeta), and CD28 signaling elements, effectively lyse tumor cells expressing PSMA. When stimulated by cell-surface PSMA, retrovirally transduced lymphocytes undergo robust proliferation, expanding by more than 2 logs in three weeks, and produce large amounts of interleukin-2 (IL-2). Importantly, the amplified cell populations retain their antigen-specific cytolytic activity. These data demonstrate that fusion receptors containing both TCR and CD28 signaling moieties are potent molecules able to redirect and amplify human T-cell responses. These findings have important implications for adoptive immunotherapy of cancer, especially in the context of tumor cells that fail to express major histocompatibility complex antigens and co-stimulatory molecules.
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PMID:Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRzeta /CD28 receptor. 1175 65

Up-regulation of receptor-ligand pairs during interaction of a peptide-bound MHC complex on dendritic cells (DCs) with cognate TCR may amplify, sustain, and drive diversity in the ensuing T cell immune response. Members of the TNF ligand superfamily and the TNFR superfamily contribute to this costimulatory molecule signaling. In the present study, we used replication deficient adenoviruses to introduce a tumor-associated Ag (a truncated human prostate-specific membrane antigen (tPSMA)) and the T cell costimulatory molecule 4-1BBL into murine DCs, and observed the ability of these recombinant DCs to elicit tPSMA-directed T-cell responses in vitro and anti-tumor immunity to RM-1-tPSMA in a murine tumor model. Infection of DCs with Ad-tPSMA-IRES-m4-1BBL induced tPSMA-specific proliferative responses and up-regulated CD80 and CD86 s signaling molecules. The cytotoxic T lymphocytes activated by the Ad-tPSMA-IRES-m4-1BBL-transfected DCs showed significantly higher IFN-gamma production and cytotoxicity against the RM-1 cells transfected with tPSMA. Moreover, vaccination of mice with Ad-tPSMA-IRES-m4-1BBL-transfected DCs induced a potent protective and therapeutic anti-tumor immunity to RM-1-tPSMA in a tumor model. These results demonstrated that development of DCs engineered to express tPSMA and 4-1BBL by recombinant adenovirus-mediated gene transfer may offer a new strategy for prostate cancer immunotherapy.
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PMID:Anti-tumor immune response induced by dendritic cells transduced with truncated PSMA IRES 4-1BBL recombinant adenoviruses. 2014 24