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Dr. Dotti studied immunotherapy strategies to treat patients with hematologic malignancies including lymphomas and leukemia and solid tumors such as neuroblastoma. In particular, he developed the program of the CD19-specific chimeric antigen receptor at Baylor College of Medicine and cloned a novel chimeric antigen receptor targeting the light chain of human immunoglobulins. This chimeric molecule engrafted in human T-lymphocytes allows a selective elimination of tumor cells expressing the kappa-light chain of human immunoglobulin while sparing the normal compartment of B-lymphocytes expressing the lambda-light chain. Dr Dotti was also involved in developing CAR-based strategies to target solid tumors such as neuroblastoma in pediatric patients and triple negative breast cancer in adult patients. In collaboration with Dr Brenner he also developed the clinical phase of a novel safety switch for T cells based on the human caspase-9. A significant focus of Dr Dotti research is the development of strategies of T cell engineering aimed at overcoming immune suppressive mechanisms of the tumor microenvironment.
Caruana I, Savoldo B, Hoyos V, Weber G, Liu H, Kim ES, Ittmann MM, Marchetti D, Dotti G. Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes. Nat Med. 2015 May;21(5):524-529.
Caruana I, Weber G, Ballard BC, Wood MS, Savoldo B, Dotti G. K562-Derived Whole-Cell Vaccine Enhances Antitumor Responses of CAR-Redirected Virus-Specific Cytotoxic-T Lymphocytes in vivo. Clin Cancer Res. 2015 Jul 1;21(13):2952-62.
Arber C, Feng X, Abhyankar H, Romero E, Wu MF, Heslop HE, Barth P, Dotti G, Savoldo B. Survivin-specific T cell receptor targets tumor but not T cells. J Clin Invest. 2015 Jan 2;125(1):157-68.
Nishio N, Diaconu I, Liu H, Cerullo V, Caruana I, Hoyos V, Bouchier-Hayes L, Savoldo B, Dotti G Armed Oncolytic Virus Enhances Immune Functions of Chimeric Antigen Receptor-Modified T Cells in Solid Tumors. Cancer Res. 2014 Sep 15;74(18):5195-205
Xu Y, Zhang M, Ramos CA, Durett A, Liu E, Dakhova O, Liu H, Creighton CJ, Gee AP, Heslop HE, Rooney CM, Savoldo B, Dotti G. Closely related T-memory stem cells correlate with in vivo expansion of CAR.CD19-T cells and are preserved by IL-7 and IL-15. Blood. 2014 Jun 12;123(24):3750-9.
Zhou X, Di Stasi A, Tey SK, Krance RA, Martinez C, Leung KS, Durett AG, Wu MF, Liu H, Leen AM, Savoldo B, Lin YF, Grilley BJ, Gee AP, Spencer DM, Rooney CM, Heslop HE, Brenner MK, Dotti G. Long-term outcome and immune reconstitution after haploidentical stem cell transplant in recipients of allodepleted-T-cells expressing the inducible caspase-9 safety transgene. Blood. 2014 Jun 19;123(25):3895-905