Pilot trial with a tetravalent conjugate vaccine against small cell lung cancer

针对小细胞肺癌的四价结合疫苗的试点试验

• 批准号: 7325719
• 负责人: PHILIP O. LIVINGSTON
• 金额: $ 20.18万
• 依托单位: MABVAX THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-25 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7325719
• 关键词: Adjuvant Chemotherapy; Agreement; Althaea; Antibodies; Antibody Formation; Antigens; Blood; Cancer Patient; Cancer Vaccines; Centers for Disease Control and Prevention (U.S.); Clinical; Clinical Trials; Conjugate Vaccines; Contracts; Disease; Dose; End Point; Enzyme-Linked Immunosorbent Assay; Foundations; Globo-H; Guanosine Monophosphate; Immunization; Individual; Institution; Keyhole Limpet Hemocyanin; Legal patent; Licensing; Local Therapy; Logistics; Malignant Neoplasms; Memorial Sloan-Kettering Cancer Center; Micrometastasis; Multicenter Trials; Neoplasm Metastasis; Operative Surgical Procedures; Patients; Pharmacologic Substance; Phase; Phase II Clinical Trials; Placebo Control; Policies; Polysialic Acid; Preparation; Radiation therapy; Randomized; Residual state; Safety; Small Business Technology Transfer Research; Surface Antigens; Technology; Technology Transfer; Testing; Time; Vaccination; Vaccine Design; Vaccine Production; Vaccines; Vial device; cancer cell; immunogenic; immunogenicity; lung small cell carcinoma; neoplastic cell; pilot trial; preclinical study; vaccine evaluation

DESCRIPTION (provided by applicant): This Phase 1 STTR application is for a pilot clinical trial of an antibody inducing tetravalent vaccine against SCLC. Its foundation is 30 years of studies during which time 1) vaccine design for optimal antibody responses against cancer cell surface antigens was determined, 2) the benefit of immunization in the minimal disease setting where circulating tumor cells and micrometastases are the primary targets was demonstrated in preclinical studies, 3) the antigens expressed by the common cancers were defined and the 4 antigens relevant for a SCLC vaccine identified, 4) the SCLC tetravalent vaccine was selected as the most promising for testing in a randomized Phase 2 trial, 5) the safety and immunogenicity of monovalent vaccines against these four antigens was confirmed and, the optimal dose of each vaccine in patients in the post chemotherapy adjuvant setting was determined, and 6) technology for vaccine production was successfully transferred to a contract GMP facility (Althea Technologies, Inc.) so that conjugates could be prepared for a multicenter Phase 2 clinical trial. The primary endpoints of the proposed pilot trial are safety and immunogenicity. Since the individual conjugates in this tetravalent vaccine were prepared under contract by GMP facilities instead of at MSKCC as in the past, and will be vialed and administered together rather than individually to separate patients, the issues of safety and immunogenicity are not trivial. If this GMP grade tetravalent vaccine proves safe and immunogenic in the pilot trial to be supported by this Phase 1 application, a Phase 2 STTR application to support the randomized, placebo-controlled Phase 2 trial will be submitted. Administered antibodies and antibodies induced by the tetravalent vaccine proposed here against small cell lung cancer (SCLC) cell surface antigens are ideally suited for eradication of free SCLC cells and micrometastasis. If antibodies of sufficient titer can be induced against these antigens to eliminate tumor cells from the blood and to eradicate micrometastasis, this would dramatically change our approach to treating the SCLC patient. Establishment of new metastasis would no longer be possible so more aggressive local therapies including surgery or radiation therapy of minimal known residual metastasis might result in long term control of even metastatic SCLC.

描述（由申请人提供）：此阶段1 STTR应用是针对抗SCLC诱导四位量疫苗的抗体的试验临床试验。它的基础是30年的研究，在此期间1）确定了针对癌细胞表面抗原的最佳抗体反应的疫苗设计，2）在最小疾病环境中免疫的益处，在旋链研究中，循环肿瘤细胞和微分光度循环是主要靶标的，在旋链研究中证明了主要靶标，3）由常见癌症识别出4型抗原的抗原，并识别出4）抗原的抗原。 tetravalent vaccine was selected as the most promising for testing in a randomized Phase 2 trial, 5) the safety and immunogenicity of monovalent vaccines against these four antigens was confirmed and, the optimal dose of each vaccine in patients in the post chemotherapy adjuvant setting was determined, and 6) technology for vaccine production was successfully transferred to a contract GMP facility (Althea Technologies, Inc.) so that conjugates could为多中心2期临床试验做好准备。拟议的试点试验的主要终点是安全性和免疫原性。由于GMP设施根据合同而不是在MSKCC的合同中制备了该四接疫苗中的各个偶联物，并且将被用瓶和给药，而不是单独使用，而不是单独用于分开的患者，因此安全性和免疫原性的问题并非微不足道。如果该GMP级四接疫苗在该阶段1应用程序中证明是安全且免疫原性的，则将提交支持随机，安慰剂控制的2期试验的2阶段STTR应用。在此提出的针对小细胞肺癌（SCLC）细胞表面抗原诱导的抗体和抗体非常适合根除自由SCLC细胞和微量分裂。如果可以针对这些抗原诱导足够的滴度抗体，以消除血液中的肿瘤细胞并消除微量表，这将极大地改变我们治疗SCLC患者的方法。建立新的转移将不再是可能的，因此更具侵略性的局部疗法，包括手术或最小已知残留转移的放射疗法，可能会导致长期控制转移性SCLC。

项目成果

Immunization with N-propionyl polysialic acid-KLH conjugate in patients with small cell lung cancer is safe and induces IgM antibodies reactive with SCLC cells and bactericidal against group B meningococci.

• DOI: 10.1007/s00262-011-1083-6
• 发表时间: 2012-01
• 期刊: CANCER IMMUNOLOGY IMMUNOTHERAPY
• 影响因子: 5.8
• 作者: Krug, Lee M.;Ragupathi, Govind;Hood, Chandra;George, Constantine;Hong, Feng;Shen, Ronglai;Abrey, Lauren;Jennings, Harold J.;Kris, Mark G.;Livingston, Philip O.
• 通讯作者: Livingston, Philip O.