Devin Mutha
- CAR-T cell therapy research
- CRISPR and Genetic Engineering
- T-cell and B-cell Immunology
- Biosimilars and Bioanalytical Methods
- Viral Infectious Diseases and Gene Expression in Insects
- Advanced biosensing and bioanalysis techniques
Caribou Biosciences (United States)
2022-2024
Allogeneic chimeric antigen receptor (CAR) T cell therapies hold the potential to overcome many of challenges associated with patient-derived (autologous) CAR cells. Key considerations in development allogeneic include prevention graft-vs-host disease (GvHD) and suppression allograft rejection. Here, we describe preclinical data supporting ongoing first-in-human clinical study, CaMMouflage trial (NCT05722418), evaluating CB-011 patients relapsed/refractory multiple myeloma. is a...
Abstract Background: CLL-1 is a compelling therapeutic target for AML as it highly expressed on tumor cells and leukemic stem but not hematopoietic cells. CB-012 was engineered with next-generation Cas12a CRISPR hybrid RNA-DNA (chRDNA) genome-editing technology leverages both checkpoint disruption immune cloaking armoring strategies to potentially improve antitumor activity. The anti-CLL-1 CAR developed fully human scFv the CD28 costimulatory domain currently in development treatment of...
<p>Antitumor activity of CB-011 CAR-T cells in a xenograft model multiple myeloma.</p>
<p>CB-011 immune-cloaking armoring strategy suppresses cytotoxic T and NK cell–mediated allograft rejection.</p>
<p>In vitro serial rechallenge assay demonstrates long-term cytotoxicity activity of CB-011 against BCMA+ tumor cells.</p>
<p>Gamma-secretase inhibitor RO4929097 increases BCMA expression on-target cell lines but does not improve CB-011 antitumor efficacy.</p>
<p>CB-011 cells exhibit in vitro antitumor activity against PBMCs from patients with multiple myeloma.</p>
<div>Abstract<p>Allogeneic chimeric antigen receptor (CAR) T cell therapies hold the potential to overcome many of challenges associated with patient-derived (autologous) CAR cells. Key considerations in development allogeneic include prevention graft-vs-host disease (GvHD) and suppression allograft rejection. Here, we describe preclinical data supporting ongoing first-in-human clinical study, CaMMouflage trial (NCT05722418), evaluating CB-011 patients relapsed/refractory...
<p>CB-011 immune-cloaking armoring strategy reduced NK cell proliferation and CAR+ T stress signatures.</p>
<div>Abstract<p>Allogeneic chimeric antigen receptor (CAR) T cell therapies hold the potential to overcome many of challenges associated with patient-derived (autologous) CAR cells. Key considerations in development allogeneic include prevention graft-vs-host disease (GvHD) and suppression allograft rejection. Here, we describe preclinical data supporting ongoing first-in-human clinical study, CaMMouflage trial (NCT05722418), evaluating CB-011 patients relapsed/refractory...
<p>In vitro serial rechallenge assay demonstrates long-term cytotoxicity activity of CB-011 against BCMA+ tumor cells.</p>
<p>Antitumor activity of CB-011 CAR-T cells in a xenograft model multiple myeloma.</p>
<p>CB-011 immune-cloaking armoring strategy suppresses cytotoxic T and NK cell–mediated allograft rejection.</p>
<p>Antitumor activity of CB-011 CAR-T cells in a xenograft model multiple myeloma.</p>
<p>chRDNA-mediated gene editing did not result in any off-target above the limit of detection.</p>
<p>chRDNA-mediated gene editing did not result in any off-target above the limit of detection.</p>
<p>Gamma-secretase inhibitor RO4929097 increases BCMA expression on-target cell lines but does not improve CB-011 antitumor efficacy.</p>
<p>CB-011 cells exhibit in vitro antitumor activity against PBMCs from patients with multiple myeloma.</p>
<p>Antitumor activity of CB-011 CAR-T cells in a xenograft model multiple myeloma.</p>
<p>CB-011 immune-cloaking armoring strategy reduced NK cell proliferation and CAR+ T stress signatures.</p>
Abstract Background: CB-012 is an allogeneic anti-CLL-1 CAR-T cell therapy in development for evaluation relapsed or refractory acute myeloid leukemia (r/r AML). engineered with a next-generation CRISPR genome-editing technology to leverage both checkpoint disruption and immune cloaking enhance persistence of antitumor activity. Methods: Caribou’s hybrid RNA-DNA (chRDNA) guides combination Cas12a were used make five edits the manufacture CB-012. A fully human CAR transgene was...
Abstract The approval and commercial launch of multiple first-generation CD19- or BCMA-directed, autologous CAR-T cell products have laid the foundation opened a path for development more advanced cellular therapeutics, including with next-generation capabilities. Among these newer designs, allogeneic therapies are positioned to unlock broad potential engineered immune cells as leading therapeutic modality. However, expansion, persistence, armoring, trafficking critical achieving long-term...