Ex Vivo Expanded Multi-Specific Cytotoxic T Lymphocytes Derived from HIV+ Patients and HIV Negative Donors Using GMP Compliant Methodologies Recognize Multiple HIV Antigens and Suppress HIV Replication

Sharon Lam, Julia A.M. Sung, Russell Cruz, Paul Castillo, Minthran Ngo, Joann Kuruc, Cliona M. Rooney, David Margolis, Catherine M. Bollard
2015 Biology of Blood and Marrow Transplantation  
balance by flow cytometry. Administration of anti-ST2 shifted Th1/Th2 balance toward a Th2 phenotype (Fig. 2 ). In addition, ST2 blockade also induced expansion of regulatory T cells (Tregs) (Fig. 2) . Given that anti-ST2 administration also up-regulated expression of genes, such as Granzyme A, that can mediate graft vs. leukemia (GVL) responses (Fig. 1E ), we postulated that ST2 blockade would not affect therapeutic GVL activity. To confirm this, we developed a clinically relevant model of
more » ... emia, in which C3H.SW recipients were challenged with syngeneic GFP+ MLL-AF9 induced acute myeloid leukemia cells. Our results indicated that administration of anti-ST2 preserved substantial GVL activity and resulted in significantly improved leukemia-free survival (Fig. 3) , suggesting that anti-ST2 ameliorated GVHD and maintained GVL response. In summary, we found that prophylaxis with anti-ST2 antibody could alleviate GVHD severity and mortality while preserving GVL effect. ST2 blockade increased the level of plasma IL-33, skewed the Th1/Th2 balance toward a Th2 phenotype, and induced Foxp3+Tregs (with preserved expression of membrane ST2 [not shown]). Our findings suggest that ST2 is a novel therapeutic target to ameliorate GVHD. Figure 2. Blockade of ST2 shifts the Th1/Th2 balance toward Th2 phenotype and increases CD4D regulatory T cells. Spleen T cells were collected for intracellular staining at day l0 post-transplantation. * p<0.05, ** p<0.01. Figure 3. Anti-ST2 mAb treatment preserves substantial GVL activity. (A) Survival cure. (B) GVHD score (bars) and percent of tumor relapse (lines). ** p<0.01, IgG vs Anti-ST2 Abstracts / Biol Blood Marrow Transplant 21 (2015) S54eS78 S64
doi:10.1016/j.bbmt.2014.11.066 fatcat:4tlxwaxlnrbbbhqelyg43nhaau