1992
DOI: 10.1073/pnas.89.4.1428
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Antibody-targeted interleukin 2 stimulates T-cell killing of autologous tumor cells.

Abstract: A genetically engineered fusion protein consisting of a chimeric anti-ganglioside GD2 antibody (chl4.18) and interleukin 2 (IL2) was tested for its ability to enhance the killing of autologous GD2-expressing melanoma target cells by a tumor-infiltrating lymphocyte line (660 TIL). The fusion of IL2 to the carboxyl terminus of the immunoglobulin heavy chain did not reduce IL2 activity as measured in a standard proliferation assay using either mouse or human T-cell lines. Antigen-binding activity was greater than… Show more

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Cited by 156 publications
(131 citation statements)
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“…Figure 1B (Fig. 1C), treatment of s.c. NXS2 tumors with hu14.18-IL2 IC administered IT also resulted in significant antitumor effects compared to PBS-treated tumors (p < 0.0015, beginning on day 11), and enhanced antitumor effects compared to the same dose of hu14.18-IL2 IC given IV (p < 0.02, days [11][12][13][14][15][16][17][18]. In addition to significant differences in the mean calculated tumor volume based on caliper measurements of length and width (see Materials and Methods section), the IT IC-treated tumors also appeared visually flatter, with less elevation above the abdominal wall, compared to either PBS or IV IC-treated tumors.…”
Section: It Ic Resulted In Greater Antitumor Effects Than IV Icmentioning
confidence: 99%
See 1 more Smart Citation
“…Figure 1B (Fig. 1C), treatment of s.c. NXS2 tumors with hu14.18-IL2 IC administered IT also resulted in significant antitumor effects compared to PBS-treated tumors (p < 0.0015, beginning on day 11), and enhanced antitumor effects compared to the same dose of hu14.18-IL2 IC given IV (p < 0.02, days [11][12][13][14][15][16][17][18]. In addition to significant differences in the mean calculated tumor volume based on caliper measurements of length and width (see Materials and Methods section), the IT IC-treated tumors also appeared visually flatter, with less elevation above the abdominal wall, compared to either PBS or IV IC-treated tumors.…”
Section: It Ic Resulted In Greater Antitumor Effects Than IV Icmentioning
confidence: 99%
“…The IL2 component of the IC augments the effects of mAb, and has been shown to increase the number and activation state of NK cells, as well as to stimulate tumor cell killing by antigen-specific T-cells [37]. In addition, the IL2 component can stimulate both NK and T-cells via the IL2 receptor, independent of Fc or T-cell receptor binding, respectively [12,28,[40][41]. Taken together, our studies suggest that the proposed mechanisms of action for systemic IC also occur when IC therapy is administered directly to the tumor microenvironment.…”
Section: Discussionmentioning
confidence: 99%
“…The application of recombinant DNA technology has recently led to the construction of antibody-cytokine fusion proteins designed to achieve optimal biological effectiveness by combining the unique targeting ability of antibodies with the multifunctional activities of cytokines (14,19,20). Antibody-cytokine fusion proteins have been proposed for the treatment of solid tumors, including melanoma (14) and Table 1.…”
Section: Discussionmentioning
confidence: 99%
“…This chl4.18-IL-2 fusion protein was shown previously to target IL-2 to tumor cells and to stimulate T-cell-mediated killing of autologous melanoma cells in vitro more effectively than equivalent amounts of rhIL-2 (14). In this report, we demonstrate the ability of the chl4.18-IL-2 fusion protein to suppress the dissemination and growth of human neuroblastoma in experimental hepatic metastases of severe combined immunodeficiency (scid) mice in the presence ofhuman LAK cells and to prolong the life-span of these animals.…”
mentioning
confidence: 99%
“…The IL-2 activity of the MK2-23-IL-2 fusion protein was assayed as described (25). Briefly, a standard T-cell proliferation assay was done using mouse CTLL-2 cells grown in DMEM supplemented with 10% FCS which had been IL-2-depleted for 48 hours before the assay.…”
Section: Introductionmentioning
confidence: 99%