Cancer regression in patients with metastatic melanoma after the transfer of autologous antitumor lymphocytes - PubMed (original) (raw)

Clinical Trial

. 2004 Oct 5;101 Suppl 2(Suppl 2):14639-45.

doi: 10.1073/pnas.0405730101. Epub 2004 Sep 20.

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Clinical Trial

Cancer regression in patients with metastatic melanoma after the transfer of autologous antitumor lymphocytes

Steven A Rosenberg et al. Proc Natl Acad Sci U S A. 2004.

Abstract

Our recent clinical trials demonstrate that autologous cell transfer after lymphodepleting chemotherapy can cause the regression of large, vascularized tumors in patients with refractory metastatic melanoma. Eighteen of 35 patients treated with tumor-reactive lymphocyte cultures experienced an objective clinical response (>50% reduction in tumor), including four complete responders. In some patients, tumor regression was accompanied by a large in vivo expansion of the administered antitumor lymphocytes, which persisted in peripheral blood at >70% of total lymphocytes for many months after transfer. The cells capable of mediating tumor regression consisted of heterogeneous lymphocyte populations with high avidity for tumor antigens that were derived from tumor-infiltrating lymphocytes cultured for limited times in vitro. The success of this treatment likely results from the ability to infuse large numbers of activated antitumor lymphocytes into an appropriate host homeostatic environment depleted of regulatory T cells. These studies are elucidating the requirements for successful immunotherapy of patients with advanced metastatic disease and are leading to additional clinical trials with gene-modified lymphocytes.

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Figures

Fig. 1.

Fig. 1.

MRI images before treatment (Left) and 2 months after cell transfer (Right) demonstrated the regression of multiple liver metastases (arrows) of patient 11 who had an overall mixed response.

Fig. 2.

Fig. 2.

Multiple lung metastases (arrows) showed dramatic shrinkage in computed tomographic scans of patient 6 who had an overall partial response to treatment. (Left) Before treatment. (Right) Seven months after cell transfer.

Fig. 3.

Fig. 3.

Regression of metastases in axillary (Top), pelvic (Middle), and mesenteric (Bottom) nodes was evident in computed tomographic scans taken before treatment (Left) or 7 months after cell transfer (Right) of patient 1, who had an overall partial response.

Fig. 4.

Fig. 4.

Patient 9 experienced an objective partial response with >95% reduction in cutaneous and s.c. disease (arrows) as seen in computed tomographic scans take before treatment (Left) or 3 months after cell transfer (Right).

Fig. 5.

Fig. 5.

Patient 31 exhibited an overall complete response with regression of multiple liver metastases as seen in computed tomographic images taken before treatment (Left) or 1 month after cell transfer (Right).

Fig. 6.

Fig. 6.

IL-2 gene transduced TILs exhibited enhanced survival in vitro. (Left) TILs transduced with the IL-2 gene linked to yellow fluorescent protein (IL-2YFP, ♦) exhibited IL-2-independent growth and survival compared to control TILs transduced with YFP alone (▪). No difference in growth rate was seen when cells were rapidly expanded with OKT3 in the presence of exogenous IL-2 (Right). In the absence of exogenously added IL-2 (Center), the IL-2-transduced cells increased in number after OKT3 stimulation, whereas the YFP-transduced control cells did not. When cells were initially expanded in OKT3 and IL-2, followed by IL-2 withdrawal (Left), the IL-2-transduced cells increased to greater numbers and remained viable for longer then the control YFP-transduced cells.

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References

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