Mark DeMario

NEO-STIM advances personalized neoantigen-specific adoptive T cell therapy

Divya Lenkala, Jessica Kohler, Brian McCarthy, Michael S. Nelson et autres

Abstract Neoantigen-based adoptive T cell therapies (ACTs) represent a promising avenue in cancer immunotherapy due to their exquisite tumor specificity. The first cell-based immunotherapy for a solid tumor, comprising tumor-infiltrating lymphocytes, recently received FDA approval. Building on this, we designed a distinct …

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Publisher Correction: Personalized, autologous neoantigen-specific T cell therapy in metastatic melanoma: a phase 1 trial

Jessica S.W. Borgers, Divya Lenkala, Victoria Kohler, Emily Jackson et autres

In the version of the article initially published, the y -axis label in Fig. 3f was incorrect and has now been amended to “% Cas3 + of live target cells”. Additionally, this article was originally published under Creative Commons Attribution 4.0 International …

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Immune modulation in solid tumors: a phase 1b study of RO6870810 (BET inhibitor) and atezolizumab (PD-L1 inhibitor)

Daniel Marbach, Jurriaan Brouer-Visser, Laura Brennan, Sabine Wilson et autres

PURPOSE: Bromodomain and extra-terminal domain (BET) inhibitors (BETi) have demonstrated epigenetic modulation capabilities, specifically in transcriptional repression of oncogenic pathways. Preclinical assays suggest that BETi potentially attenuates the PD1/PD-L1 immune checkpoint axis, supporting its combination with immunomodulatory agents. PATIENTS AND METHODS: A …

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Personalized, autologous neoantigen-specific T cell therapy in metastatic melanoma: a phase 1 trial

Jessica S.W. Borgers, Divya Lenkala, Victoria Kohler, Emily Jackson et autres

Abstract New treatment approaches are warranted for patients with advanced melanoma refractory to immune checkpoint blockade (ICB) or BRAF-targeted therapy. We designed BNT221, a personalized, neoantigen-specific autologous T cell product derived from peripheral blood, and tested this in a 3 + 3 …

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Immune Modulation in Solid Tumors: A Phase 1b Study of RO6870810 (BET Inhibitor) and Atezolizumab (PD-L1 Inhibitor)

Daniel Marbach, Jurriaan Brouer-Visser, Laura Brennan, Sabine Wilson et autres

ABSTRACT Purpose Bromodomain and extra-terminal domain (BET) inhibitors (BETi) have demonstrated epigenetic modulation capabilities, specifically in transcriptional repression of oncogenic pathways. Preclinical assays suggest that BETi potentially attenuates the PD1/PD-L1 immune checkpoint axis, supporting its combination with immunomodulatory agents. Patients and Methods …

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BNT321, a novel monoclonal antibody targeting sialyl Lewis A: Phase 1 monotherapy and combination with mFOLFIRINOX in patients with advanced CA19-9 expressing cancers.

Eileen M. O’Reilly, Todd M. Bauer, Erkut Borazanci, Meredith Pelster et autres

654 Background: BNT321 is a high affinity human monoclonal antibody targeting the sialyl Lewis A epitope of CA19-9. This Phase 1/1b dose escalation/expansion study investigated BNT321 as monotherapy and in combination with mFOLFIRINOX (mFFX) in patients (pts) with advanced CA19-9 expressing cancers. …

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769 Interim clinical and translational data from NTC-001, a phase I study to evaluate the non-engineered neoantigen-specific T cell product BNT221 in patients with advanced or metastatic melanoma

Jessica S.W. Borgers, Divya Lenkala, Brian P. McCarthy, Victoria Kohler et autres

Background Neoantigens, tumor-specific antigens derived from the mutanome, elicit antitumor immune responses. The interim results of a phase I study (NCT04625205) evaluating a personalized, non-engineered, neoantigen-specific T-cell product (BNT221) targeting multiple neoantigens are presented. Methods Nine patients with checkpoint- and, if applicable, …

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1017O NTC-001: A phase I study to test safety and efficacy of BNT221, a non-engineered neoantigen-specific T cell product, in patients with advanced or metastatic melanoma

Jessica S.W. Borgers, Divya Lenkala, Brian J. McCarthy, Victoria Kohler et autres

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Data from A Phase I Monotherapy Study of RG7212, a First-in-Class Monoclonal Antibody Targeting TWEAK Signaling in Patients with Advanced Cancers

Ulrik Lassen, Didier Meulendijks, L.L. Siu, Vaios Karanikas et autres

Abstract Purpose: Tumor necrosis factor (TNF)–like weak inducer of apoptosis (TWEAK) and fibroblast growth factor-inducible molecule 14 (Fn14) are a ligand–receptor pair frequently overexpressed in solid tumors. TWEAK:Fn14 signaling regulates multiple oncogenic processes through MAPK, AKT, and NFκB pathway activation. A phase …

Supplementary Table 1 from RG7212 Anti-TWEAK mAb Inhibits Tumor Growth through Inhibition of Tumor Cell Proliferation and Survival Signaling and by Enhancing the Host Antitumor Immune Response

Xuefeng Yin, Leopoldo Luistro, Hua Zhong, Melissa Smith et autres

PDF file, 29K, Lead antibodies have identical binding properties and neutralizing activities.

Supplementary Figure 3 from RG7212 Anti-TWEAK mAb Inhibits Tumor Growth through Inhibition of Tumor Cell Proliferation and Survival Signaling and by Enhancing the Host Antitumor Immune Response

Xuefeng Yin, Leopoldo Luistro, Hua Zhong, Melissa Smith et autres

PDF file, 771K, TWEAK promotes proliferation and survival signaling with minimal effect on cell viability.

Supplementary Figure 1 from RG7212 Anti-TWEAK mAb Inhibits Tumor Growth through Inhibition of Tumor Cell Proliferation and Survival Signaling and by Enhancing the Host Antitumor Immune Response

Xuefeng Yin, Leopoldo Luistro, Hua Zhong, Melissa Smith et autres

PDF file, 306K, RG7212 antitumor efficacy and characterization of tumor models used to assess RG7212 antitumor efficacy.