Bartnes K
Avdeling for hjerte-/lunge-/karkirurgi Regionsykehuset i Tromsø 9038 Tromsø.
Tidsskr Nor Laegeforen. 2001 Oct 20;121(25):2941-5.
Due to acquired mutations, the protein composition of malignant tumours is distinct from that of normal cells to which the immune system is tolerant. Mobilisation of the patient's immune system against malignant cells remaining after conventional treatment is an attractive therapeutic option since lymphocytes respond with high sensitivity and specificity to non-self.
The potential of cancer vaccines targeted to T helper cells is discussed on the basis of published data including the author's studies.
T helper cells kill cancer cells by direct cell-cell contact, stimulate other cytotoxic effector cells and respond to autologous tumour antigens like HER-2/neu (mammary and ovary cancer), tyrosinase (malignant melanoma), p21 ras (colorectal and pancreatic cancer), BCR-ABL (chronic myeloid leukaemia) and immunoglobulin (B-cell lymphoma). HER-2/neu and tyrosinase are not mutated, p21 ras and BCR-ABL represent a restricted set of mutations, and genetic variants of immunoglobulin can be characterised by hybridoma technology.
Targeted screening can, in a large number of cancer patients, identify peptide sequences potentially useful for therapeutic immunisation. Peptides can be designed to combine immunogenicity in the individual patient with proteolytic resistance, and are presently being tested as cancer vaccines.
由于获得性突变,恶性肿瘤的蛋白质组成与免疫系统所耐受的正常细胞不同。动员患者的免疫系统对抗传统治疗后残留的恶性细胞是一种有吸引力的治疗选择,因为淋巴细胞对非自身物质具有高敏感性和特异性反应。
基于已发表的数据(包括作者的研究)讨论了靶向辅助性T细胞的癌症疫苗的潜力。
辅助性T细胞通过直接的细胞间接触杀死癌细胞,刺激其他细胞毒性效应细胞,并对自体肿瘤抗原如HER-2/neu(乳腺癌和卵巢癌)、酪氨酸酶(恶性黑色素瘤)、p21 ras(结直肠癌和胰腺癌)、BCR-ABL(慢性髓性白血病)和免疫球蛋白(B细胞淋巴瘤)产生反应。HER-2/neu和酪氨酸酶没有突变,p21 ras和BCR-ABL代表一组有限的突变,免疫球蛋白的基因变体可用杂交瘤技术进行表征。
在大量癌症患者中,靶向筛查能够识别出可能对治疗性免疫有用的肽序列。肽可以设计成在个体患者中兼具免疫原性和蛋白水解抗性,目前正作为癌症疫苗进行测试。