Berd David
Department of Medicine, Kimmel Cancer Center, Thomas Jefferson University, 1015 Walnut Street, Suite 1024, PA 19107, USA.
Expert Rev Vaccines. 2004 Oct;3(5):521-7. doi: 10.1586/14760584.3.5.521.
The author has devised a novel approach to the immunotherapy of cancer based on modification of autologous tumor cells with the hapten, dinitrophenyl (DNP). This technology is being developed by AVAX Technologies (MO, USA) as a treatment for melanoma under the brand name, M-Vax. The treatment program consists of multiple intradermal injections of DNP-modified autologous tumor cells mixed with bacille Calmette-Guerin as an immunological adjuvant. Administration of DNP vaccine to patients with metastatic melanoma induces a unique reaction--the development of inflammation in metastatic masses. Following DNP-vaccine treatment, almost all patients develop delayed-type hypersensitivity (DTH) to autologous, DNP-modified melanoma cells and about half also exhibit DTH to autologous, unmodified tumor cells. The toxicity of the vaccine is mild, consisting mainly of papules or pustules at the injection sites. Clinical trials have been conducted in two populations of melanoma patients: Stage IV with measurable metastases, and clinical Stage III patients rendered tumor-free by lymphadenectomy. There were 11 antitumor responses in 83 patients with measurable metastases: two complete, four partial and five mixed. In 214 Stage III patients the 5-year overall survival rate was 44%, which compares favorably with the reported surgical rate of 20-25%. In both populations, the induction of DTH to unmodified autologous tumor cells was associated with significantly longer survival. This is a platform technology that is adaptable to other human cancers and early trials indicate immunological activity in ovarian and renal cell carcinomas.
作者设计了一种基于用半抗原二硝基苯基（DNP）修饰自体肿瘤细胞的癌症免疫治疗新方法。这项技术正由AVAX技术公司（美国密苏里州）以M-Vax的品牌开发用于治疗黑色素瘤。治疗方案包括多次皮内注射与卡介苗混合的DNP修饰的自体肿瘤细胞，卡介苗作为免疫佐剂。给转移性黑色素瘤患者接种DNP疫苗会引发一种独特的反应——转移灶出现炎症。接受DNP疫苗治疗后，几乎所有患者对自体、DNP修饰的黑色素瘤细胞产生迟发型超敏反应（DTH），约一半患者对自体未修饰的肿瘤细胞也表现出DTH。疫苗的毒性较轻，主要表现为注射部位出现丘疹或脓疱。已在两类黑色素瘤患者中进行了临床试验：有可测量转移灶的IV期患者，以及通过淋巴结清扫术实现无瘤状态的临床III期患者。83例有可测量转移灶的患者中有11例出现抗肿瘤反应：2例完全缓解，4例部分缓解，5例混合缓解。在214例III期患者中，5年总生存率为44%，与报道的20%-25%的手术生存率相比更具优势。在这两类患者中，对未修饰的自体肿瘤细胞诱导产生DTH与显著更长的生存期相关。这是一种可应用于其他人类癌症的平台技术，早期试验表明其在卵巢癌和肾细胞癌中具有免疫活性。
