J Pharm Pharmacogn Res 2(Suppl. 1): S6, 2014
Special supplement with the abstract book of LATINFARMA 2013
CO 011: PRECLINICAL EVIDENCES OF P3 MAB IMMUNORESTORATION CAPACITY ON SUPPRESSED BALB/C MICE
Martínez D, Rodríguez-Zhurbenko N, Griñan T, Rondón T, Vázquez AM, Hernández AM.
Introduction: A fast reconstitution of T cell dependent immunity is a critical issue for patients treated with lymphodepleting regimens. Prolonged period of T cell dysfunction may have serious consequences for the patients, like higher susceptibility to infections, reduced response to vaccines and easier tumor relapse. P3, a murine IgM mAb, recognize N-glycolilated gangliosides, sulphatides and antigens expressed in several human tumors. This antibody has the ability to trigger an IgG antibody response in the syngeneic Balb/c model, even when it is administered without adjuvant or carrier protein. Although the mechanism by which the P3 activates the immune system is unknown, previous experiments show that it is capable of stimulate T cells populations.
Material and methods: We evaluate the importance of T cell populations in the P3 mAb immunogenicity and the capacity of P3 to recover T cells populations on immunosuppressed Balb/c mice, due to tumor or cyclophosphamide treatment.
Results: We show that the high immunogenicity of P3 mAb depends not only on CD4+ but also on CD8+ T cells, since the depletion of CD8+ or CD4+ T cells led to the loss of P3 mAb immunogenicity in the syngeneic model. Furthermore, the immunization with P3 mAb enhanced the recovery of the CD8+ T cell population in mice treated with an anti-CD8a antibody. Additionally, the immunization with P3 mAb restored the capacity of immunosuppressed mice to reject allogeneic tumors, a mechanism mediated by the action of CD8+ T cells. Finally, in mice with cyclophosphamide induced lymphopenia, the administration of P3 mAb accelerated the recovery of both CD4+ and CD8+ T cells.
Conclusions: These results show new possibilities for B and CD8+ T cells interactions during the immune response elicited by a self-protein. Furthermore they point to P3 mAb as a potential interesting candidate for the treatment of immunosuppressed patients.