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Combination therapy for head and neck cancer with CTL induced in vitro and low dose of anticancer drugs followed by iradiation.

Combination therapy for head and neck cancer with CTL induced in vitro and low dose of anticancer drugs followed by iradiation.
体外诱导 CTL 和低剂量抗癌药物随后进行放射治疗的头颈癌联合治疗。
批准号:
06454490
负责人:
ISHIKAWA Takeru
金额:
$4.1万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B)
财政年份:
1994
资助国家:
日本
项目状态:
已结题
起止时间:
1994 至 1996

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中文摘要
翻译
对22例上颌窦癌(MSC)患者采用低剂量化疗和过继免疫联合治疗2个周期。采集外周血单个核细胞(PBMC)后第4、5天,将导管逆行插入肿瘤供血动脉。次日动脉内注射顺铂或卡铂,剂量分别为20 mg/体、100 mg/体,5-氟尿嘧啶250 mg/体,连续5天。在低剂量化疗期间,利用同种异体间充质干细胞和白细胞介素-2从自体PBMC诱导细胞毒性T淋巴细胞(CTL)。在完成低剂量化疗后,这些体外诱导的CTL被输注回动脉内给患者,并通过CT扫描评估其效果。根据三种联合治疗的评价,所有患者均行40次放射治疗,再行手术治疗。在22例患者中,分别有1例和14例对化学免疫治疗表现出完全缓解(CR)和部分缓解(PR)。共有13例(55%)患者在三种联合治疗后出现临床CR。在这13例临床CR患者中,有11例在组织学上未发现残留肿瘤,需要手术治疗,且功能和形态学上均无明显牺牲。两例组织学上的PR患者尽管术后进行了额外的照射,但仍发生了复发。9例PR患者均行除眶术1例,其余3例和5例分别行上颌切除术(保留眶内容物)和Denker手术(同时保留眶内容物和上颚),7例复发。Kaplan-Meier生存率显示患者5年生存率约为60%。三种联合治疗为大约一半的MSC患者带来了疗效和良好的生活质量。
英文摘要
We applied 2 cycles of combination therapy with low dose chemotherapy and adoptive immunotherapy for 22 patients with maxillary sinus carcinoma (MSC). On 4th or 5th day after collection of peripheral blood mononuclear cells (PBMC), cannula were inserted retrogradely into tumor feeding artery. On the following day, cisplatin or carboplatin was injected intraarterially at 20 mg/body, 100 mg/body, respectively and 250 mg/body of 5-fluorouracil were administered on the subsequent 5 consecutive days. During the low dose chemotherapy, cytotoxic T lymphocyte (CTL) were induced from autologous PBMC using allogeneic MSC cell line and interleukin-2. After the completion of low dose chemotherapy, these in vitro-induced CTL were infused back intra-arterially to the patient, and the effects were estimated by CT scans. Subsequently, all the patients received 40 Gy-radiotherapy and then surgery on the basis of the evaluation on the three combination therapy. Of 22 patients, one and fourteen showed complete response (CR) and partial response (PR), respectively, to the chemo-immunotherapy. A total of 13 patients (55%) showed clinical CR in response to the three combined therapy. No residual tumor was confirmed histollogically in eleven of these thirteen clinical CR patients and required surgery without pitiful functional and morphological sacrifices. The two histlological PR patients occurred recurrence despite additional post-operative irradiation. In 9 clinical PR patients, surgery including orbital exenteration was carried out for one patients and the other 3 and 5 patients received maxillectomy (preserved orbital content) and Denker's operation (preserved both orbital content and palate), respectively and 7 occurred recurrence. Kaplan-Meier survival rate showed that 5 year survival rate of these patients were approximately 60%. The three combination therapy brought curative effect and good quality of life to approximately half of MSC patients.
期刊论文(52)
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会议论文
Kazuaki Chikamatsu,et al: "The role of major histocompatibility complex expression on head and neck cancer cells in the induction of autologous cytotoxic Tlymphocytes." Cancer Immunol Immunother. 38. 358-364 (1994)
Kazuaki Chikamatsu 等人:“头颈癌细胞上主要组织相容性复合物表达在诱导自体细胞毒性 T 淋巴细胞中的作用。”
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通讯作者:
Kang Das Lee et al: "Expression of the MAGE-1,-2,-3,-4,and -6 genes in non-squamous cell carcinomalesions of the head and neck." Acta Otolaryngol(Stockh). 116. 633-639 (1996)
Kang Das Lee 等人:“MAGE-1、-2、-3、-4 和 -6 基因在头颈部非鳞状细胞癌病变中的表达”。
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江浦正郎 他: "頭頚部悪性腫瘍と腫瘍免疫" JOHNS. 12. 106-111 (1996)
Masao Eura 等:“头颈恶性肿瘤和肿瘤免疫”JOHNS. 12. 106-111 (1996)
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石川 哮: "リンパ球を用いた癌免疫療法-頭頚部扁平上皮癌に対するキラーT療法の現状-" 医薬の門社, 7 (1996)
Ren Ishikawa:“使用淋巴细胞的癌症免疫疗法 - 头颈鳞状细胞癌的杀伤性 T 疗法的现状” Iyaku no Monsha,7 (1996)
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52
    Study on induction of autologous CTL by mixed culture with allogeneic tumor cells.
    • 批准号:
      02454397
    • 项目类别:
      Grant-in-Aid for General Scientific Research (B)
    • 资助金额:
      $3.52万
    • 财政年份:
      1990
    • 负责人:
      ISHIKAWA Takeru
    • 依托单位:
    Investigation of immunologic heterogeneity of primary head and neck cancer and its cervical metastases.
    • 批准号:
      61480359
    • 项目类别:
      Grant-in-Aid for General Scientific Research (B)
    • 资助金额:
      $3.01万
    • 财政年份:
      1986
    • 负责人:
      ISHIKAWA Takeru
    • 依托单位:
    海外基金