Melanoma and Skin Cancer Program SPORE

项目摘要摘要：总体 皮肤癌是美国最常见的癌症，包括黑色素瘤和皮肤鳞状细胞癌 癌(CSCC)。尽管取得了实质性进展，但大多数晚期黑色素瘤患者并未受益于 虽然最有效的治疗黑色素瘤的方法也会导致严重的不良事件。此外，我们仍然 需要对免疫能力和免疫缺陷患者进行安全、有效和成本效益高的CSCC治疗 这可能会改变这些高危患者群体的治疗和结果。该计划的总体目标 黑色素瘤和皮肤癌计划(MSCP孢子)是开发新的翻译研究，以克服 黑色素瘤和皮肤鳞状细胞癌目前治疗的障碍。这三个项目中的每一个都是由开创性和 MSCP孢子研究人员的创新发现，这些发现被翻译成新的 黑色素瘤和皮肤癌患者的联合免疫治疗试验。项目1将评估 抗LAG3单独和联合抗PD1的临床和免疫学活性首次在 治疗-未接受过ICB治疗的幼稚议员。项目2将评估其疗效和免疫原性。 Ⅱ/Ⅲ期PD1幼稚转移性黑色素瘤中A型CpG的cMP-001(CMP)的研究 肿瘤内使用CMP和nivolumab(CMP/Nivo)与Nivo的随机临床试验。项目3将测试一部小说 微针阵列(MNA)装置，可同时输送诱导免疫原细胞的有效化疗药物 死亡和一种先天免疫刺激剂转化为可接近的cscc。此方法将在以下两个方面进行测试 免疫活性和免疫抑制癌症患者。MSCP孢子将使用创新策略 以确定对建议的治疗方案的反应和抵抗机制。调查人员将会 由共享设施核心支持，提供最先进的专业知识和规模经济示例 收集和处理、翻译病理学、数据注释、生物谱库和 免疫监测(核心1)；和2)生物统计和生物信息学(核心2)，支持严谨和 所有研究项目的重现性。职业提升计划(CEP)与发展 研究计划(DRP)将吸引有才华的基础、翻译和临床研究人员进入黑色素瘤 研究。MSCP孢子利用希尔曼癌症中心(HCC)的资源和机构承诺 拥有最先进的研究和临床设施，临床监管服务支持临床试验 协调和翻译研究。MSCP孢子包括杰出的外部和内部 咨询委员会(EAB、IAB)，一个在成功的 管理孢子和患者代言人。MSCP孢子的组织结构将 促进全面跟踪进度并管理每个项目的潜在障碍。MSCP孢子 将与科学界和其他孢子分享数据，以符合NIH的政策。MSCP 孢子将受益于并促进与学术机构的大量横向和纵向合作 机构、NCI、制药公司和合作团体。

Project Summary Abstract: Overall Skin cancers are the most common cancers in the US, including melanoma and cutaneous squamous cell carcinoma (cSCC). Despite substantial progress, most patients with advanced melanoma do not benefit from treatment, while the most potent therapies of melanoma also cause serious adverse events. In addition, we still need safe, efficient, and cost-effective therapies of cSCCs in immunocompetent and immunodeficient patients that could transform treatment and outcomes for these at-risk patient populations. The overall goal of the Melanoma and Skin Cancer Program (MSCP SPORE) is to develop novel translational research to overcome the hurdles of current therapies of melanoma and cSCCs. Each of the three Projects results from seminal and innovative findings made by the investigators of the MSCP SPORE, which are translated into new combinatorial immunotherapy trials for patients with melanoma and skin cancers. Project 1 will assess the clinical and immunological activity of anti-LAG3 alone and in combination with anti-PD1, for the first time, in treatment-naïve MPs who have not received prior ICB. Project 2 will evaluate the efficacy, and immunogenicity of CMP-001 (CMP), a type A CpG, in PD1 naïve metastatic melanoma in the context of a phase II/III randomized clinical trial with intratumoral CMP and nivolumab (CMP/nivo) vs. nivo. Project 3 will test a novel microneedle array (MNA) device to deliver both a potent chemotherapeutic agent to induce immunogenic cell death and an innate immune stimulant into accessible cSCCs. This approach will be tested both in immunocompetent and immunosuppressed cancer patients.The MSCP SPORE will use innovative strategies to determine the mechanisms of response and resistance to the proposed therapies. The investigators will be supported by shared-facility cores to provide state-of-the-art expertise and economies-of-scale in 1) sample collection and processing, translational pathology, data annotation, biospecimen repository, and immunomonitoring (Core 1); and 2) biostatistics and bioinformatics (Core 2), supporting rigor and reproducibility across all research projects. The Career Enhancement Program (CEP) and Development Research Program (DRP) will attract talented basic, translational, and clinical investigators into melanoma research. The MSCP SPORE leverages Hillman Cancer center (HCC) resources and institutional commitment with state-of-the-art research and clinical facilities, clinical regulatory services to support clinical trial coordination, and translational research. The MSCP SPORE includes outstanding External and Internal Advisory Boards (EAB, IAB), an Executive Committee that is highly experienced in the successful management of SPOREs and Patient Advocates. The organizational structure of the MSCP SPORE will facilitate thorough following of progress and managing of potential hurdles for each project. The MSCP SPORE will share data with the scientific community and other SPOREs in agreement with the NIH policy. The MSCP SPORE will benefit from and promote a large number of horizontal and vertical collaborations with academic institutions, NCI, pharmaceutical companies, and cooperative groups.