- Allison J.P., McIntyre B.W., Bloch D. Tumor-specific antigen of murine T-lymphoma defined with monoclonal antibody. J Immunol 129:2293-2300; 1982.
The first identification of the T cell antigen receptor (TCR).
- McIntyre B.W., Allison J.P. The mouse T cell receptor: structural heterogeneity of molecules of normal T cells defined by xenoantiserum. Cell 34:739-746; 1983.
The first detailed structure of the T cell antigen receptor protein showing it to be a disulfide-linked heterodimer with constant and variable peptides on both chains.
- Harding F.A., McArthur J.G., Gross J.A., Raulet D.H., Allison J.P. CD28-mediated signaling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Nature 356: 607-609; 1992.
Identification of CD28 as the T cell receptor for costimulatory signals required, in addition to the TCR, for activation of naïve T cells and prevention of anergy, opening the door to molecular studies of costimulation.
- Krummel M.F., Allison J.P. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J Exp Med 182:459-465; 1995.
This paper showed that the CD28 homolog CTLA-4 is not a costimulator, as was generally accepted at the time, but rather acts as an inhibitor of T cell activation, the first known cell intrinsic inhibitory pathway.
- Leach D.R., Krummel M.F., Allison J.P. Enhancement of antitumor immunity by CTLA-4 blockade. Science 271:1734-1736; 1996.
This paper showed that blockade of the inhibitory effects of CTLA-4 in vivo is sufficient to obtain rejection and durable immunity to tumors of diverse histology and proposed the notion of immune checkpoint blockade in cancer therapy. It led to several patents and the clinical development and ultimate FDA approval of ipilimumab for the treatment of both metastatic and adjuvant melanoma. This led to acceptance of immunotherapy as a pillar of cancer treatment and the new paradigms of immune checkpoint blockade and immune-oncology.
- van Elsas A., Hurwitz A.A., Allison J.P. Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation. J Exp Med 190:355-366; 1999.
Showed that combination of CTLA-4 blockade and a genetically modified tumor cell vaccine were synergistic in treatment of a poorly immunogenic tumor.
- Peggs K.S., Quezada S.A., Chambers C.A., Korman A.J., Allison J.P. Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies. J Exp Med 206: 1717-1725; 2009.
This paper largely resolved a controversy regarding the cellular targets and mechanism of action of anti-CTLA-4 by showing that targeting only regulatory CD4 T cells had no anti-tumor effects, but targeting effector CD4 T cells provided anti-tumor responses, which were further enhanced with the addition of blockade of CTLA-4 on regulatory T cells.
- Curran M.A., Montalvo W., Yagita H., Allison J.P. PD-1 and CTLA-4 combination blockade expands infiltrating T-cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci U S A 107:4275-4280; 2010.
This preclinical study showed that a combination of anti-CTLA-4 and antibodies to a second immune checkpoint, PD-1, were additive, presaging a clinical study reported in 2013 showing a 50% response rate in metastatic melanoma and subsequent FDA approval of this combination in the treatment of metastatic melanoma.
- Fan X., Quezada S.A., Sepulveda M.A., Sharma P., Allison J.P. Engagement of the ICOS pathway markedly enhances efficacy of CTLA-4 blockade in cancer immunotherapy. J Exp Med 211:715-725; 2014.
This pre-clinical study showed that agonistic stimulation of ICOS, a costimulatory receptor on the surface T cells expressed after anti-CTA-4 treatment, could greatly enhance the efficacy of CTLA-4 blockade, a finding that has led to a patent and the clinical development of agonistic ICOS antibody by several pharmaceutical companies
- Zamarin D., Holmgaard R.B., Subudhi S.K., Park J.S., Mansour M., Palese P., Merghoub T., Wolchok J.D., Allison, J.P. Localized oncolytic virotherapy overcomes systemic tumor resistance to immune checkpoint blockade immunotherapy. Sci Transl Med 6:226ra32; 2014.
This paper showed that local delivery of the oncolytic Newcastle Disease Virus, together with intraperitoneal delivery of anti-CTLA-4, resulted in rejection of distant tumors, leading to a patent which has been licensed to a pharmaceutical company for clinical development.
- Wei S.C., Levine J.H., Cogdill A.P., Zhao Y., Anang N.A.S., Andrews M.C., Sharma P., Wang J., Wargo J.A., Pe'er D., Allison J.P. Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade. Cell. 170(6):1120-1133; 2017.
This paper identified more than 15 tumor-infiltrating T cell populations and determined that anti-CTLA-4 and anti-PD-1 utilize distinct cellular mechanisms, suggesting the possibility of combinatorial treatments.