Botensilimab, an Fc-enhanced anti-CTLA-4 antibody, is effective against tumors poorly responsive to conventional immunotherapy

This dataset contains the binding affinity measurements of the various mouse anti-CTLA-4 (αCTLA-4) antibodies to mouse Fc gamma receptors as determined by surface plasmon resonance. It also includes calculated activating to inhibitory (A/I) ratios for each antibody. This information is crucial for understanding the Fc-mediated effector functions of the αCTLA-4 antibodies used in the study, providing insight into their in vivo efficacy and mechanisms of action.

This dataset contains the binding affinity measurements of the botensilimab and the corresponding parental IgG1 anti-CTLA-4 antibody to human Fc gamma receptors as determined by surface plasmon resonance. It also includes calculated activating to inhibitory (A/I) ratios for each antibody.

This table presents a comparison of the binding epitopes of botensilimab, ipilimumab, and tremelimumab on human CTLA-4. It highlights the specific amino acid residues on CTLA-4 that are involved in the binding interface for each antibody. This comparison provides insight into binding characteristics of botensilimab relative to established anti-CTLA-4 therapies.

This dataset summarizes the toxicology findings from a 13-week repeat-dose study of botensilimab in cynomolgus monkeys. This comprehensive toxicology profile is crucial for assessing the safety of botensilimab, and is particularly relevant for predicting potential human toxicity.

This dataset presents the serum pharmacokinetic parameters of botensilimab in cynomolgus monkeys. The study includes both male and female monkeys, allowing for sex-based comparisons. These data are crucial for understanding botensilimab's behavior in the body and inform dose selection for clinical trials. The dataset provides insights into potential differences in drug metabolism between sexes and across different dose levels. Importantly, it also helps contextualize the toxicology findings, allowing for a more comprehensive assessment of the drug's safety and efficacy profile.

This dataset provides an overview of the baseline demographic characteristics of patients with advanced solid tumors who participated in the ongoing phase 1 trial of botensilimab. This demographic information is crucial for understanding the patient population studied and is valuable for interpreting the safety and efficacy outcomes of the study.

This dataset summarizes the clinical response and disease control rates of patients with advanced solid tumors treated in the ongoing phase 1 trial of botensilimab. These efficacy measures are crucial for assessing the therapeutic potential of botensilimab alone and in combination with balstilimab. Importantly, these data further highlight the therapeutic potential in patients who have progressed on prior immune checkpoint therapy, providing valuable insights into botensilimab's efficacy in this challenging-to-treat population.

This dataset summarizes the best overall response of each patient reported in the manuscript. It offers insights into clinical responses to botensilimab alone and in combination with balstilimab across various advanced solid tumor types. Importantly, it includes data on patients who progressed on prior conventional immune checkpoint therapy or have tumor types historically non-responsive to immunotherapy. By providing a patient-level view of treatment efficacy, this dataset allows for a nuanced understanding of how different tumor types and individual patients respond to botensilimab.

This dataset summarizes the grade 3 or higher treatment-related adverse events (TRAEs) observed in patients with advanced solid tumors treated in the ongoing phase 1 trial of botensilimab. This safety information is crucial for assessing the risk-benefit profile of botensilimab alone and in combination with balstilimab.

This key resource table provides a comprehensive list of all antibodies and proteins used in the study, thus allowing other researchers to accurately replicate or conduct similar studies using the same reagents.

This table provides technical information about the multiplex immunofluorescence studies performed using the Akoya Biosciences CODEX platform. This is crucial for the reproducibility and interpretation of the multiplex immunofluorescence results.

This dataset presents the binding characteristics of the mouse anti-CTLA-4 (αCTLA-4) antibodies to various mouse Fc gamma receptors (FcγRs). This information is crucial for understanding the Fc-mediated effector functions of the αCTLA-4 antibodies used in the study. The binding data help explain the mechanisms of action and potential efficacy differences between the various αCTLA-4 antibodies in mouse models.

This dataset presents comparative results demonstrating the enhanced efficacy of Fc-enhanced anti-CTLA-4 versus the parental anti-CTLA-4 antibody in various tumor-bearing mouse models. Data from multiple tumor-bearing mouse models, strengthens the generalizability of the findings across different tumor types. The individual mouse data allows for a detailed view of treatment responses, including, variability within treatment groups, timing and rate of tumor growth or regression and potential identification of exceptional responders or non-responders.

This dataset presents comparative results demonstrating the enhanced T cell modulation in the tumor microenvironment promoted by Fc-enhanced anti-CTLA-4 versus the parental anti-CTLA-4 antibody in two specific tumor-bearing mouse models: MC38 and CT26. These data demonstrate the superior ability of Fc-enhanced anti-CTLA-4 to promote T cell infiltration and Treg depletion in the tumor microenvironment. This information is crucial for understanding the mechanistic basis for the improved anti-tumor efficacy of Fc-enhanced anti-CTLA-4 antibodies.

This dataset presents comparative results demonstrating the superior ability of Fc-enhanced anti-CTLA-4 to potentiate antigen-specific T cell responses in vivo versus the parental anti-CTLA-4 antibody. The use of the Staphylococcal Enterotoxin B-challenged model in non-tumor bearing mice highlights the broader immunological effects of Fc-enhanced anti-CTLA-4 beyond the tumor microenvironment.

This dataset presents the pharmacokinetic (PK) profile of mouse Fc-enhanced anti-CTLA-4 antibody versus the parental anti-CTLA-4 antibody. The PK profile is important for interpreting the efficacy data, and further supports the conclusion that the enhanced anti-tumor effects are likely due to the engineered Fc-mediated functions rather than altered drug exposure or persistence in the body.

This dataset presents results demonstrating the broad combination activity of Fc-enhanced anti-CTLA-4 in various poorly immunogenic tumor-bearing mouse models. It demonstrates the potential of Fc-enhanced anti-CTLA-4 antibodies to improve outcomes in various combination treatment strategies, supporting their broad applicability in cancer immunotherapy.

This dataset provides detailed information on the binding characteristics and functional properties of botensilimab. This comprehensive dataset demonstrates botensilimab's high affinity and selectivity for CTLA-4, its ability to effectively block CTLA-4 interactions with its ligands comparable to that of the parental IgG1 anti-CTLA-4 antibody. Importantly, this data further supports that the superior functional attributes of botensilimab are due to the Fc-engineered region and not the variable region of the antibody.

This dataset provides a comprehensive analysis of the Fcγ receptor binding kinetics and Fc-mediated functions of botensilimab compared to other approved anti-CTLA-4 antibodies. These results highlight the unique Fc-mediated properties of botensilimab, particularly its enhanced engagement of activating Fcγ receptors without inducing complement-dependent cytotoxicity. This data further provides mechanistic insights into botensilimab's potential for enhanced immune modulation and anti-tumor efficacy.

This dataset presents results showing the effect of botensilimab on CD4+ non-regulatory T cells (non-Tregs) in stimulated human peripheral blood mononuclear cell (PBMC) cultures. It demonstrates that unlike conventional anti-CTLA-4, botensilimab treatment does not lead to a decrease in CD4+ non-Treg populations in stimulated human PBMC cultures. This information is crucial for understanding botensilimab's unique mechanism of action and its potential advantages over conventional IgG1 anti-CTLA-4 antibodies. Importantly, these results further support the hypothesis that under context of antigen-stimulation, botensilimab decreases the generation of Tregs rather than promoting depletion via antibody-dependent cellular cytotoxicity. This mechanism distinguishes botensilimab from conventional anti-CTLA-4 antibodies and may account for its superior T cell responsiveness and activation.

This dataset provides important insights into botensilimab's effects on the myeloid compartment of the immune system. The increase in CD11c+ HLA-DR+ myeloid cells, which likely represent antigen-presenting cells, suggests that botensilimab may enhance antigen presentation and T cell activation. The lack of effect on CD16- myeloid cells indicates a selective impact on specific myeloid subsets. These findings contribute to understanding botensilimab's unique mechanism of action, suggesting it may enhance anti-tumor immunity not only through effects on T cells but also by modulating myeloid cell populations.

This CONSORT flow diagram for the expanded phase I clinical trial of botensilimab is essential for assessing the validity and generalizability of the trial results. It allows readers to understand how many patients were initially considered, how many were actually treated, and how many contributed to the biomarker analyses. This transparency is essential for interpreting the strength of the evidence supporting botensilimab's efficacy and safety in advanced solid cancers.

This figure describes the flow cytometry gating strategy used for T cell immune profiling in cryopreserved peripheral blood mononuclear cells (PBMCs) from patients with advanced solid cancers treated with botensilimab. The gating strategy allows for a comprehensive analysis of various CD4+ T cell subpopulations.

This dataset presents additional evidence of botensilimab's immunological effects on peripheral T cell activation in patients with advanced solid cancers. It demonstrates dose-dependent increases in key T cell activation markers. These findings provide further insight into botensilimab's mechanism of action, offer potential biomarkers for treatment monitoring, and support its dose-response relationship. The data further help researchers and clinicians better understand botensilimab's immunomodulatory potential in cancer treatment.

This dataset presents analysis of intratumoral regulatory T cells (Tregs) and CD8+ T cells in tumor biopsies from patients with advanced solid cancers before and after botensilimab treatment. Importantly, these data further support and confirm the changes previously reported by deconvolution analyses of RNA sequencing data. This corroboration between protein-level staining and transcriptomic analyses provides robust evidence of botensilimab's effects on the tumor immune microenvironment, offering valuable insights into its mechanism of action and potential to enhance anti-tumor immunity.

This dataset shows that response to botensilimab, alone or with balstilimab, in patients with advanced cancers is independent of tumor neoantigen burden and FcγRIIIA allele status. This suggests that botensilimab's efficacy may be broad and not limited by these commonly used biomarkers typically associated with response to conventional immune checkpoint therapy. The data highlights a potential advantage of botensilimab over traditional immunotherapies, indicating it might be effective in a wider range of patients, including those who may not typically respond to standard checkpoint inhibitors.

This dataset examines the relationship between FCGR2A and FCGR3A gene expression and clinical response to anti-PD-1 or conventional anti-CTLA-4 therapies in patients with advanced melanoma. Analysis of multiple clinical trial datasets shows that response to these conventional immunotherapies is not associated with FCGR2A or FCGR3A expression levels. This contrasts with botensilimab's efficacy profile, supporting its unique Fc-dependent mechanism of action. The data further support that FCGR2A and FCGR3A expression could be predictive biomarkers of response to botensilimab, distinguishing it from conventional immunotherapies.

This dataset analyzes the relationship between FCGR2A and FCGR3A gene expression and immune cell type enrichment in tumor biopsies from patients treated with botensilimab alone or in combination with balstilimab. The analysis provides insights into the immune landscape associated with FCGR2A and FCGR3A expression in the tumor microenvironment, suggesting potential cellular mechanisms underlying botensilimab's efficacy. This data supports the role of FCGR2A and FCGR3A as potential biomarkers and helps elucidate how their expression may relate to specific immune cell infiltration patterns relevant to botensilimab's unique Fc-dependent mechanism of action.