Therapeutic efficacy of tumor-targeted IL2 in LTalpha(-/-) mice depends on conditioned T cells.
An effective immunological eradication of tumors by the adaptive immune system depends on T cell priming, expansion of specific T cells and their effector function. It has been shown that either step may be impaired in the tumor-bearing host, and several strategies have been used to improve antitumor immune responses. In this regard, tumor-targeted IL2 therapy leads to the destruction of established melanoma metastases in fully immune competent mice as previously demonstrated. This effect has been attributed, but never directly confirmed, to the boost of antigen-experienced T cells. To this end, we demonstrate the absence of any antitumor effect of targeted IL2 in mice characterized by an impaired priming of T cell responses. Notably, in these animals tumor-targeted IL2 therapy induced tumor regression only after adoptive transfer of tumor-conditioned splenocytes. A detailed analysis revealed that T cells present within the transferred splenocytes were actively participating in the immune response as these were clonally expanded after targeted IL2 therapy. In summary, we demonstrate here that in LTalpha(-/-) mice lacking sufficient numbers of tumor-specific T cells only the passive transfer of such cells prior to therapy restores the efficacy of tumor-targeted IL2 therapy. Thus, the antitumor effect of tumor-targeted IL2 is indeed based on the boost of pre-existing T cell responses.
Schrama
David
D
Department of Dermatology, Julius Maximilians-University, 97080, Würzburg, Germany.
Voigt
Heike
H
Eggert
Andreas O
AO
Xiang
Rong
R
Reisfeld
Ralph A
RA
Becker
Jürgen C
JC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D002999:Clone Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D016503:Drug Delivery Systems; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy; D008233:Lymphotoxin-alpha / Q000172:deficiency* / Q000235:genetics; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000627:therapeutic use; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology; D040521:Subcutaneous Tissue; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D008233:Lymphotoxin-alpha; D011993:Recombinant Fusion Proteins; C112746:dinutuximab