ORCID Profile
0000-0002-6797-9511
Current Organisation
Medizinische Universität Wien
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Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.C.6532800.V1
Abstract: AbstractPurpose: Advanced-stage gastrointestinal cancers represent a high unmet need requiring new effective therapies. We investigated the antitumor activity of a novel T cell–engaging antibody (B7-H6/CD3 ITE) targeting B7-H6, a tumor-associated antigen that is expressed in gastrointestinal tumors. Experimental Design: Membrane proteomics and IHC analysis identified B7-H6 as a tumor-associated antigen in gastrointestinal tumor tissues with no to very little expression in normal tissues. The antitumor activity and mode of action of B7-H6/CD3 ITE was evaluated in i in vitro /i coculture assays, in humanized mouse tumor models, and in colorectal cancer precision cut tumor slice cultures. Results: B7-H6 expression was detected in 98% of colorectal cancer, 77% of gastric cancer, and 63% of pancreatic cancer tissue s les. B7-H6/CD3 ITE-mediated redirection of T cells toward B7-H6–positive tumor cells resulted in B7-H6–dependent lysis of tumor cells, activation and proliferation of T cells, and cytokine secretion in i in vitro /i coculture assays, and infiltration of T cells into tumor tissues associated with tumor regression in i in vivo /i colorectal cancer models. In primary patient-derived colorectal cancer precision-cut tumor slice cultures, treatment with B7-H6/CD3 ITE elicited cytokine secretion by endogenous tumor-infiltrating immune cells. Combination with anti-PD-1 further enhanced the activity of the B7-H6/CD3 ITE. Conclusion: These data highlight the potential of the B7-H6/CD3 ITE to induce T cell–redirected lysis of tumor cells and recruitment of T cells into noninflamed tumor tissues, leading to antitumor activity in i in vitro, in vivo /i , and human tumor slice cultures, which supports further evaluation in a clinical study. /
Publisher: American Association for Cancer Research (AACR)
Date: 27-09-2022
DOI: 10.1158/1078-0432.CCR-22-2108
Abstract: Advanced-stage gastrointestinal cancers represent a high unmet need requiring new effective therapies. We investigated the antitumor activity of a novel T cell–engaging antibody (B7-H6/CD3 ITE) targeting B7-H6, a tumor-associated antigen that is expressed in gastrointestinal tumors. Membrane proteomics and IHC analysis identified B7-H6 as a tumor-associated antigen in gastrointestinal tumor tissues with no to very little expression in normal tissues. The antitumor activity and mode of action of B7-H6/CD3 ITE was evaluated in in vitro coculture assays, in humanized mouse tumor models, and in colorectal cancer precision cut tumor slice cultures. B7-H6 expression was detected in 98% of colorectal cancer, 77% of gastric cancer, and 63% of pancreatic cancer tissue s les. B7-H6/CD3 ITE-mediated redirection of T cells toward B7-H6–positive tumor cells resulted in B7-H6–dependent lysis of tumor cells, activation and proliferation of T cells, and cytokine secretion in in vitro coculture assays, and infiltration of T cells into tumor tissues associated with tumor regression in in vivo colorectal cancer models. In primary patient-derived colorectal cancer precision-cut tumor slice cultures, treatment with B7-H6/CD3 ITE elicited cytokine secretion by endogenous tumor-infiltrating immune cells. Combination with anti-PD-1 further enhanced the activity of the B7-H6/CD3 ITE. These data highlight the potential of the B7-H6/CD3 ITE to induce T cell–redirected lysis of tumor cells and recruitment of T cells into noninflamed tumor tissues, leading to antitumor activity in in vitro, in vivo, and human tumor slice cultures, which supports further evaluation in a clinical study.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.C.6532800
Abstract: AbstractPurpose: Advanced-stage gastrointestinal cancers represent a high unmet need requiring new effective therapies. We investigated the antitumor activity of a novel T cell–engaging antibody (B7-H6/CD3 ITE) targeting B7-H6, a tumor-associated antigen that is expressed in gastrointestinal tumors. Experimental Design: Membrane proteomics and IHC analysis identified B7-H6 as a tumor-associated antigen in gastrointestinal tumor tissues with no to very little expression in normal tissues. The antitumor activity and mode of action of B7-H6/CD3 ITE was evaluated in i in vitro /i coculture assays, in humanized mouse tumor models, and in colorectal cancer precision cut tumor slice cultures. Results: B7-H6 expression was detected in 98% of colorectal cancer, 77% of gastric cancer, and 63% of pancreatic cancer tissue s les. B7-H6/CD3 ITE-mediated redirection of T cells toward B7-H6–positive tumor cells resulted in B7-H6–dependent lysis of tumor cells, activation and proliferation of T cells, and cytokine secretion in i in vitro /i coculture assays, and infiltration of T cells into tumor tissues associated with tumor regression in i in vivo /i colorectal cancer models. In primary patient-derived colorectal cancer precision-cut tumor slice cultures, treatment with B7-H6/CD3 ITE elicited cytokine secretion by endogenous tumor-infiltrating immune cells. Combination with anti-PD-1 further enhanced the activity of the B7-H6/CD3 ITE. Conclusion: These data highlight the potential of the B7-H6/CD3 ITE to induce T cell–redirected lysis of tumor cells and recruitment of T cells into noninflamed tumor tissues, leading to antitumor activity in i in vitro, in vivo /i , and human tumor slice cultures, which supports further evaluation in a clinical study. /
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22488723.V1
Abstract: Supplementary Figure 1 (A) OGAP® Screen of tumor and non-tumorous (normal, non-diseased tissues). (B) B7-H6 mRNA expression in gastrointestinal cancer tissues (TCGA). Supplementary Figure 2 B7-H6 expression on cell lines Supplementary Figure 3 Influence of B7-H6/CD3 ITE on the B7-H6-induced activation of NK-92® MI cells. Supplementary Figure 4 Pharmacokinetic profile in NOG mice.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22488723
Abstract: Supplementary Figure 1 (A) OGAP® Screen of tumor and non-tumorous (normal, non-diseased tissues). (B) B7-H6 mRNA expression in gastrointestinal cancer tissues (TCGA). Supplementary Figure 2 B7-H6 expression on cell lines Supplementary Figure 3 Influence of B7-H6/CD3 ITE on the B7-H6-induced activation of NK-92® MI cells. Supplementary Figure 4 Pharmacokinetic profile in NOG mice.
No related grants have been discovered for Carina Binder.