Li-fen Lee

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Pieter Goossens

Maastricht University, Faculty of Health Medicine and Life sciences

Amir Manbachi

Johns Hopkins University

Rock Mancini

Miami University

Philemon Mukarno

Codarts

Nathan Mathewson

Dana-Farber Cancer Institute

Iris Estrada

Instituto Politecnico Nacional

P. Bruhns

Institut Pasteur de Paris

Alireza Hedayatfar

Iran University of Medical Sciences

George R Barclay

University of Edinburgh

Mauricio Rojas

Universidad de Antioquia

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Data from Combination of 4-1BB Agonist and PD-1 Antagonist Promotes Antitumor Effector/Memory CD8 T Cells in a Poorly Immunogenic Tumor Model

Immunotherapies targeting the programmed death 1 (PD-1) coinhibitory receptor have shown great pr... more Immunotherapies targeting the programmed death 1 (PD-1) coinhibitory receptor have shown great promise for a subset of patients with cancer. However, robust and safe combination therapies are still needed to bring the benefit of cancer immunotherapy to broader patient populations. To search for an optimal strategy of combinatorial immunotherapy, we have compared the antitumor activity of the anti–4-1BB/anti–PD-1 combination with that of the anti–PD-1/anti–LAG-3 combination in the poorly immunogenic B16F10 melanoma model. Pronounced tumor inhibition occurred only in animals receiving anti–PD-1 and anti–4-1BB concomitantly, while combining anti–PD-1 with anti–LAG-3 led to a modest degree of tumor suppression. The activity of the anti–4-1BB/anti–PD-1 combination was dependent on IFNγ and CD8+ T cells. Both 4-1BB and PD-1 proteins were elevated on the surface of CD8+ T cells by anti–4-1BB/anti–PD-1 cotreatment. In the tumor microenvironment, an effective antitumor immune response was in...

Supplementary Figures 1 - 5 from Combination of 4-1BB Agonist and PD-1 Antagonist Promotes Antitumor Effector/Memory CD8 T Cells in a Poorly Immunogenic Tumor Model

Supplementary Figure S1. Anti-4-1BB and anti-PD-1 synergized to suppress B16F10 tumor growth. Sup... more Supplementary Figure S1. Anti-4-1BB and anti-PD-1 synergized to suppress B16F10 tumor growth. Supplementary Figure S2. The flow cytometric gating strategy to analyze immune cells. Supplementary Figure S3. Elevated expression of genes associated with anti-tumor immune response in MC38 colon carcinomas. Supplementary Figure S4. Accumulation of CD8+ T cell and memory phenotype differentiation in MC38 model. Supplementary Figure S5. Serum liver enzyme levels and hematology alterations in response to 4-1BB activation therapy in B16F10 tumor-bearing mice.

144: Receptor occupancy and internalization of an anti-IL-7 receptor antibody

Cytokine, 2013

In vitro (or ex vivo) quantification of cellular parameters is often employed to inform systems m... more In vitro (or ex vivo) quantification of cellular parameters is often employed to inform systems models that define the relationship between drug exposure and response. We developed two flow cytometry based assays to evaluate the interaction between the IL-7 receptor (IL-7R) and an anti-IL-7R monoclonal antibody (Ab1). IL-7R occupancy and rate of internalization in the presence of Ab1 was determined using flow cytometry in monkeys and human whole blood. Two commercially available antibodies were used to detect IL-7R. One detected “free” and the other determined “total” receptor. Receptor internalization was measured ex vivo at various time points at 37 °C. The receptor occupancy assay was used in vivo following administration of Ab1 into cynomolgus monkeys at 0.3, 3, and 30 mg/kg. The amount of Ab1 bound to receptor and the total amount of receptor was quantified. The ex vivo receptor occupancy mean IC50 values in monkey and human whole blood were 5.64 ± 2.38 and 9.39 ± 1.54 ng/ml, r...

1090: Interleukin-8 Stimulates Androgen-Independent Growth of Androgen Dependent LNCaP Cells

Journal of Urology, 2004

tolerability of treatment. Secondary endpoints include evaluation of the PSMAspecific immune resp... more tolerability of treatment. Secondary endpoints include evaluation of the PSMAspecific immune responses and treatment effect manifest by change in serum PSA levels. CONCLUSIONS: The outcomes of this study will guide development of the rsPSMA protein and VRP-PSMA vaccines used alone and/or in prime-boost combinations.

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