Immunotherapy aims at exploiting our natural immune defense mechanisms in order to either induce clearance of infected and cancer cells, or downmodulate deleterious activation of immune cells (eg in the context of allotransplantation and autoimmunity). Although immunotherapy has revolutionized the therapeutic handling of several chronic inflammatory diseases, it has yielded disappointing results in many other instances, due in particular to our yet uncomplete understanding of the mechanisms underlying tumor immune escape and allograft rejection. Beyond these conceptual limitations, implementation of immunotherapies has been hampered by more general technical and industrial constraints linked to the complex design of immunotherapeutic approaches. In particular cellular approaches rely on production of cellular preparations that are not fully characterized and standardized, and their vivo outcome is seldom assessed and poorly controlled. Moreover many approaches relying on the use of bioreagents would benefit from a less empirical selection of antigens and adjuvants, improved access to clinical grade compounds, and relevant cost-efficient in vivo models for rapid obtention of preclinical proof of efficacy. Finally, pharmaceutical constraints currently hamper industrial development of combination therapies which might be required to relieve resistance to immunotherapy, but involving molecules not validated yet as monotherapy. To meet the above challenges and develop innovative immunotherapies with enhanced efficacy, the Labex “Immunotherapy Graft Oncology” aims at fostering transdisciplinary projects between teams with complementary expertise in transplantation and tumor immunology, tumor cell survival pathways and nuclear oncology, in order to

(i) accelerate identification of new immunotherapeutic and theranostic targets in oncology, transplantation and autoimmunity,

(ii) improve standardization, efficacy and monitoring of cellular immunotherapy protocols, and

(iii) broaden the clinical indications of existing immunomodulating or immunodepleting therapies and design novel strategies with enhanced efficacy, based in particular on combination approaches or radioimmunotherapy.