Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Anticancer Res. 2011 Nov;31(11):3995-4005.
We performed continuous dendritic cells (DCs) vaccination to treat a patient with chemotherapy-resistant recurrent rectal carcinoma and lung and bone metastases. A patient has received a total of 66 DC vaccinations at 14-day intervals for 3 years until his death. Necrotic whole tumor cells (WTC) were selected as the tumor-associated antigen source because they showed a greater capacity for DC maturation and interleukin-12 secretion than both necrotic tumor lysate alone and necrotic tumor cell fragment alone. After the sixth vaccination, both skin test and interferon-γ (IFN-γ) enzyme-linked immunospot (ELISPOT) response by peripheral blood T-cells to WTC-pulsed DCs were positive. Importantly, T-cell responses were positive towards DCs pulsed with several synthetic peptides including Carcinoembryonic antigen (CEA), Melanoma associated antigen (MAGE)1 and MAGE3. A biopsy specimen collected from the pelvic bone metastasis after the 6th vaccination showed marked necrotic change of the carcinoma cells, with many infiltrating mononuclear cells. The patient did not show any particular adverse reactions to vaccination such as autoimmune phenomena. Our experience of this case suggests that continuous long-term vaccination with autologous WTC-pulsed DCs can elicit in vivo T-cell response against multiple tumor-associated antigens and induce tumor regression in disease that has proven resistant to intensive chemo- or radiation therapy.
我们对一名化疗耐药的复发性直肠癌伴肺和骨转移患者进行了连续树突状细胞（DC）疫苗接种治疗。该患者共接受了 66 次 DC 疫苗接种，每 14 天一次，持续 3 年，直至死亡。选择坏死的全肿瘤细胞（WTC）作为肿瘤相关抗原源，因为它们比单纯坏死肿瘤裂解物和单纯坏死肿瘤细胞碎片具有更强的 DC 成熟和白细胞介素-12 分泌能力。第六次接种后，外周血 T 细胞对 WTC 脉冲 DC 的皮肤试验和干扰素-γ（IFN-γ）酶联免疫斑点（ELISPOT）反应均为阳性。重要的是，T 细胞反应对包括癌胚抗原（CEA）、黑色素瘤相关抗原（MAGE）1 和 MAGE3 在内的几种合成肽脉冲的 DC 呈阳性。第 6 次接种后从骨盆骨转移部位采集的活检标本显示癌细胞出现明显的坏死变化，有许多浸润的单核细胞。患者对疫苗接种没有任何特别的不良反应，如自身免疫现象。我们对该病例的经验表明，用自体 WTC 脉冲 DC 进行连续长期疫苗接种可以在体内诱导针对多种肿瘤相关抗原的 T 细胞反应，并在已被证明对强化化疗或放疗耐药的疾病中诱导肿瘤消退。
