Novel treatment strategies for human lymphoid neoplasms using superantigen-induced apoptosis.

MARICEF VERGARA-RUBIO; MERCEDES PASTORINI; DANIELA MONTAGNA; ALEJANDRA DUARTE; ALEMAN MECEDES

Congreso; ALACI22 -13th Latin American and Caribbean Immunology and 7th Cuban Immunology Society; 2022

Novel treatment strategies for human lymphoid neoplasms using superantigen-induced apoptosisMaricefVergara-Rubio1,2, Mercedes Pastorini1,3, Daniela Montagna4, Alejandra Duarte1,5andMercedes Alemán1.1.-Laboratorio de Inmunología Experimental. IMEX-CONICET-ANM, Buenos Aires, Argentina2.-Departamento de Biología, Facultad de Ciencias. ULA, Mérida, Venezuela3.-Universidad Nacional de Quilmes. Argentina4.-Laboratorio de OncologíaExperimental. IMEX-CONICET-ANM, Buenos Aires, Argentina5.-Fundación Barceló. Argentina*e-mail: maricefv@gmail.comAlthough immunotherapy is playing an increasing role in oncohematological treatment and monoclonal antibodies are accepted in therapeutic schemes, few antigens associated exclusively to the tumor are known, so most antibodies are directed towards antigens also present in normal tissues. In contrast to conventional antigens, superantigens (SAgs) are proteins of viral or bacterial origin, which interact only with constant T-cell antigen receptor (TCR) and B-cell antigen receptor (BCR) sites. Previously our group demonstrated for the first time that bacterial and MMTV-encoded SAgs can specifically induce in vitro and in vivo death by apoptosis of T lymphoma cells expressing reactive Vβ chains, significantly increasing survival in mice, achieving more than 90% complete remission of the disease. Similar results were obtained with the PpL protein, which was able to induce apoptosis of murine B κ+ lymphoma cell lines. Based on these findings, we decided to study the capacity of SAgs to induce apoptosis in human leukemic cells, for which we used the Jurkat cell line, and we observed that Staphylococcus aureus enterotoxin E (SEE), which interacts specifically with the Vβ8 region, induces apoptosis in these cells, a mechanism that involves Fas-FasL. Also, wecorroborated an increase annexin V+ Daudi cells when using PpL (100 μg/ml), in addition to SpA. Our approach is not based on the usual immunological therapies, but on the hypothesis that neoplastic B and T cells expressing a certain chain in their receptor, retain the ability to respond specifically to SAgs by inducing strong signaling leading to death by apoptosis