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Hybrid cell, useful as therapeutic vaccine against cancer and viral, bacterial and protozoal infections, comprises allogeneic dendritic cells fused to autologous non-dendritic cells
Hybrid cell, useful as therapeutic vaccine against cancer and viral, bacterial and protozoal infections, comprises allogeneic dendritic cells fused to autologous non-dendritic cells
A hybrid cell (I) comprising a mature dendritic cell (DC) fused to a non-dendritic cell which is freshly isolated or obtained from a primary cell culture and where DC and non-DC are allogeneic to each other, is new. Independent claims are also included for the following: (1) making (M1) (I) comprising subjecting a population of mature DCs and non-DCs allogeneic to the DCs to conditions that promote cell fusion; (2) a kit comprising a sample containing a population of mature DCs in one or more containers and instructions for its use in treating or preventing cancer or an infectious disease or in making (I); (3) treating or preventing (M2) cancer or an infectious disease in a mammal comprising administering a therapeutically active amount of (I) which shares at least one class I major histocompatibility complex (MHC) allele with the mammal; and (4) preventing a cancer in an individual having a predisposition for the cancer comprising M2 where the non-dendritic cell displays the antigenicity of an antigen associated with the cancer. - ACTIVITY : Cytostatic; Antibacterial; Virucide; Protozoacide; Antiparasitic. The effect of the hybrid cells as vaccines for treating cancer was studied in 17 patients with renal cell carcinoma. The hybrid cells were formed by electrofusion of 5 X 10 to the power of 7 autologous cells derived from renal cell carcinoma tissue with 5 X 10 to the power of 7 allogeneic dendritic cells. After electrofusion and irradiation with 200 Gy, the vaccine was immediately injected. Freshly-prepared booster vaccinations were administered after 6 weeks, followed by a re-evaluation of the patients 6 weeks later. After 13 months, 4 patients completely rejected all metastatic tumor lesions, one presented a mixed response, and 2 had a tumor mass reduction of greater than 50%. This demonstrated induction of human leukocyte antigen (HLA)-A2-restricted cytotoxic T cells reactive with the MucI tumor-associated antigen and recruitment of CD8+ lymphocytes into tumor challenge sites. The hybrid cell vaccination was well tolerated by all patients and there were no serious adverse effects. These results indicated that hybrid cell vaccination was a safe and effective therapy for renal cell carcinoma. - MECHANISM OF ACTION : Vaccine.
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机译：杂种细胞（I）是新的，该杂种细胞（I）包括与非树突状细胞融合的成熟树突状细胞（DC），该树突状细胞是从原代细胞培养物中新鲜分离或获得的，并且其中DC和非DC是异源的。还包括以下方面的独立权利要求：（1）制作（M1）（I），包括使同种异体的成熟DC和非DC群体经受DC促进细胞融合的条件; （2）试剂盒，其包含在一个或多个容器中包含一批成熟DC的样品，以及其在治疗或预防癌症或传染病或制备（I）中的使用说明; （3）在哺乳动物中治疗或预防（M2）癌症或感染性疾病，包括给予与该哺乳动物共享至少一个I类主要组织相容性复合物（MHC）等位基因的治疗有效量（I）; （4）在具有包括M2的癌症易感性的个体中预防癌症，其中所述非树突细胞显示与所述癌症相关的抗原的抗原性。 -活动：细胞抑制;抗菌;杀病毒剂;原虫;抗寄生虫。在17例肾细胞癌患者中研究了混合细胞作为疫苗治疗癌症的效果。通过将5 X 10电融合至7>来自肾细胞癌组织的自体细胞的力量与5 X 10电融合至7>同种异体树突状细胞的力量来形成杂交细胞。电融合并用200 Gy照射后，立即注射疫苗。 6周后进行新鲜准备的加强免疫，然后6周后对患者进行重新评估。 13个月后，有4例患者完全排斥了所有转移性肿瘤病变，其中1例表现出混合反应，2例肿瘤缩小了50％以上。这证明了与MucI肿瘤相关抗原反应的人白细胞抗原（HLA）-A2限制性细胞毒性T细胞的诱导和CD8 +淋巴细胞募集进入肿瘤攻击位点。所有患者对混合细胞疫苗的耐受性都很好，并且没有严重的不良反应。这些结果表明，混合细胞疫苗接种是治疗肾细胞癌的安全有效方法。 -作用机理：疫苗。
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