Matis L A, Shu S, Groves E S, Zinn S, Chou T, Kruisbeek A M, Rosenstein M, Rosenberg S A
J Immunol. 1986 May 1;136(9):3496-501.
The successful adoptive immunotherapy of the syngeneic Friend virus-induced murine leukemia FBL-3 was mediated by a proliferative MHC-restricted, tumor-specific CTL clone in combination with recombinant human IL 2. This clone was previously shown to express the L3T4-, Lyt-1+, Lyt-2+ surface phenotype. Activation of the clone for 48 hr in vitro with irradiated tumor cells induced the expression of IL 2 receptors and markedly increased clonal proliferation in response to recombinant IL 2. Intravenous injection of 2 X 10(7) 48 hr in vitro-activated cloned cells, followed by 6 days of systemic (i.p.) administration of IL 2 resulted in the complete regression of tumors and the cure of 50% of the treated mice. IL 2 alone had no effect on tumor growth, whereas the injection of nonactivated (resting) clone plus IL 2 or activated clone without IL 2 had small but insignificant effects on tumor growth and survival. These results indicated that the in vivo effector functions of cloned T cells may be markedly enhanced by the concurrent systemic administration of recombinant IL 2 and by the induction of optimal IL 2 receptor expression on the cloned T cells at the time of cell administration.
同基因Friend病毒诱导的小鼠白血病FBL-3的成功过继免疫疗法是由一个增殖性的、受MHC限制的肿瘤特异性CTL克隆与重组人白细胞介素2联合介导的。该克隆先前已被证明表达L3T4-、Lyt-1+、Lyt-2+表面表型。用经照射的肿瘤细胞在体外激活该克隆48小时可诱导白细胞介素2受体的表达,并显著增加其对重组白细胞介素2的克隆增殖反应。静脉注射2×10⁷个经体外48小时激活的克隆细胞,随后连续6天全身(腹腔内)给予白细胞介素2,可导致肿瘤完全消退,50%的受试小鼠被治愈。单独使用白细胞介素2对肿瘤生长没有影响,而注射未激活(静止)的克隆细胞加白细胞介素2或激活的克隆细胞不加白细胞介素2对肿瘤生长和存活有微小但不显著的影响。这些结果表明,在细胞给药时,通过同时全身给予重组白细胞介素2以及在克隆的T细胞上诱导最佳的白细胞介素2受体表达,可显著增强克隆T细胞的体内效应功能。