Immunomodulatory biomaterial to enhancing T-cell responses to triple negative breast cancer

免疫调节生物材料可增强 T 细胞对三阴性乳腺癌的反应

基本信息

批准号：
10699815
负责人：
Fatemeh Sadat Majedi
金额：
$ 39.96万
依托单位：
SYMPHONY BIOSCIENCES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10699815
关键词：
4T1 Abscopal effect Adjuvant Adverse effects Affect Alginates Antibodies Autoimmune Biocompatible Materials Biological Sciences Biomedical Engineering Biopsy Breast Cancer Model CAR T cell therapy Canis familiaris Caring Cells Certification Cessation of life Clinical Trials Cytotoxic T-Lymphocytes Data Development Devices Distant Distant Metastasis Drug Kinetics Early treatment Endowment Exons Flow Cytometry Formulation Funding Goals Hematologic Neoplasms Histology Human Immune Immune system Immunity Immunologics Immunotherapy Implant In Situ Incubators Infiltration LoxP-flanked allele Lymphocyte Lymphoma Malignant Neoplasms Mechanics Metastatic breast cancer Modality Mus Myelogenous Neoadjuvant Therapy Neoplasm Metastasis Operative Surgical Procedures Outcome Performance Phase Pilot Projects Porifera Rattus Regulatory T-Lymphocyte Secure Site Solid Neoplasm T cell response T-Cell Activation T-Lymphocyte Techniques Testing Time Toxic effect Transforming Growth Factor beta Translating Tumor Suppression United States Work arm biocompatible polymer biodegradable polymer cancer infiltrating T cells chemotherapy cytokine release syndrome design effector T cell engineered T cells exhaustion experience fighting immunoregulation improved inhibitor innovation lymph nodes malignant breast neoplasm manufacturability manufacture melanoma mouse model neoplastic cell novel therapeutics particle patient derived xenograft model polyoma middle tumor antigen pre-Investigational New Drug meeting recruit response scaffold side effect standard of care triple-negative invasive breast carcinoma tumor tumor microenvironment tumor-immune system interactions

项目摘要

Project Summary Deaths from solid tumors vastly outnumber deaths from hematopoietic cancers. Yet progress in immunotherapies for solid tumors is well behind those for lymphoma. CAR-T cell therapies and engineered T cells have become revolutionary approaches for hematopoietic cancers, but their potential for solid tumors is yet to be realized. Significant challenges hinder the potential of immune therapies in solid tumors, including insufficient activation and eventual exhaustion of effector T cells; and suppression of T cell effector responses in the tumor microenvironment. In this proposal we consider these hurdles and offer a biomaterial solution that overcomes them. This proposal is significant in facilitating endogenous T cells to fight solid tumors. Surgery is a major treatment modality for both invasive and in situ tumors, but at this time, there are no specific immunotherapies initiated at the time of surgery; they all start days to weeks later. Our proposal is significant for offering a way to start treatments early, right at the time of initial surgery. Here our synthetic scaffold, SymphNode can be injected at the time of biopsy or surgery not to only recruit and active tumor-experienced local immune cells but also to suppress the inhibitory cells created by tumor cells. Our long-term goal is to develop this bioengineered, locally injected, “synthetic lymph node” into a therapy for human tumors.

项目概要实体瘤的死亡人数远远超过造血系统癌症的死亡人数。实体瘤的免疫疗法远远落后于淋巴瘤和 CAR-T 细胞疗法。工程化 T 细胞已成为治疗造血癌症的革命性方法，但它们的实体瘤的潜力尚未实现，重大挑战阻碍了其潜力。实体瘤的免疫疗法，包括激活不足和最终耗尽效应 T 细胞；以及抑制肿瘤微环境中的 T 细胞效应反应。在这个提案中，我们考虑了这些障碍，并提供了克服这些障碍的生物材料解决方案。该提议对于促进内源性 T 细胞对抗实体瘤具有重要意义。侵袭性和原位肿瘤的主要治疗方式，但目前还没有具体的治疗方法免疫疗法在手术时开始；我们的建议是在几天到几周后开始。对于提供一种在初次手术时尽早开始治疗的方法具有重要意义。我们的合成支架 SymphNode 可以在活检或手术时注射，不仅招募并激活经历过肿瘤的局部免疫细胞，同时也抑制抑制细胞我们的长期目标是开发这种生物工程的、局部注射的、 “合成淋巴结”成为人类肿瘤的疗法。