Cancer patients' lymphocytes contain CD3+CD4+cells that proliferate in response to autologous tumor cells in the presence of exogenous low-dose interleukin-2 and autologous accessory cells

1989 ◽  
Vol 30 (4) ◽  
pp. 233-238 ◽  
Author(s):  
Marina Radrizzani ◽  
Michele Quaia ◽  
Barbara Benedetti ◽  
Salvatore Andreola ◽  
Maurizio Vaglini ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Tumor Cells ◽  
Low Dose ◽  
Interleukin 2 ◽  
Autologous Tumor ◽  
Cd4 Cells ◽  
Accessory Cells

A phase II clinical study of dendritoma vaccination combined with low dose interleukin-2 in advanced melanoma patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3051-3051
Author(s):  
Y. C. Wei ◽  
J. J. Stephenson ◽  
J. Li ◽  
K. E. Burgin ◽  
H. Bouton-Verville ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Tumor Cells ◽  
Phase Ii ◽  
Low Dose ◽  
Interleukin 2 ◽  
Advanced Melanoma ◽  
Mixed Response ◽  
Small Phase ◽  
Clinical Responses ◽  
Melanoma Patients

3051 Background: The use of the fusion product of dendritic cells (DC) and tumor cells as a tumor vaccine represents one of the most promising approaches for cancer immunotherapy. We have developed a novel technology that instantly isolates the hybrids (Dendritomas) from the fusion mixture of DCs and tumor cells and thereby maintains tumor cellular diversity. Animal studies demonstrated that Dendritomas are superior activators of tumor cell specific antitumor immunity compared to fusion mixtures; and phase I clinical studies in advanced melanoma and renal cell carcinoma patients demonstrated that Dendritomas can be safely administered to cancer patients and are able to stimulate immunological and clinical responses in some of the patients. Methods: In order to determine the efficacy of Dendritoma vaccines, we designed a small phase II clinical trial in which individualized Dendritomas are manufactured from and injected into 15 stage IV melanoma patients. In order to boost the antitumor immune responses, a low dose interleukin-2 regime was followed only after the first Dendritoma vaccine. The patients received various numbers of vaccines (1 to 6) at six-week intervals. Clinical responses defined as complete response (CR), partial response (PR), stable disease (SD), mixed response (MR), progressive disease (PD), and no evidence of disease (NED) are monitored. The survival of the patients are monitored as well. Results: Twelve weeks after the first vaccine, three patients were NED; four patients were SD; two patients were PD/MR; and six patients were PD. At the time of the submission of this abstract, two patients were still NED and the median survival was 684 days with twelve of the fifteen patients (80%) surviving more than 431 days and eleven of fifteen patients (73%) surviving more than 519 days. Seven out of fifteen patients (47%) are still alive. Conclusions: The data from this small phase II study demonstrated that Dendritoma therapy combined with low dose IL-2 or other adjuvants may represent an effective therapy for melanoma patients and/or other cancer patients. No significant financial relationships to disclose.

scholarly journals Discordant effect of interferon on natural killer activity and tumor cell sensitivity to lysis in hairy cell leukemia

Blood ◽  
1988 ◽  
Vol 71 (4) ◽  
pp. 1141-1143 ◽  
Author(s):  
N Lahat ◽  
E Aghai ◽  
A Kotler ◽  
A Kinarty ◽  
E Sobel ◽  
...  
Keyword(s):  
Natural Killer ◽  
Tumor Cells ◽  
Hairy Cell Leukemia ◽  
Interleukin 2 ◽  
Blocking Effect ◽  
Autologous Tumor ◽  
Nk Activity ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Killer Activity

Abstract We studied the action of alpha-interferon (IFN) and interleukin-2 (IL- 2) on natural killer (NK)-rich fractions and autologous tumor cells from two patients with hairy cell leukemia (HCL). The addition of IFN or IL-2 to the NK-rich fractions resulted in a significant increase in NK activity against the autologous tumor cells. This stimulatory effect was blocked if the target hairy cells (HCs) were preincubated with either IFN or IL-2. Pretreatment of the HCs with anti-Tac antibody entirely prevented the blocking effect of IL-2 and partially the blocking effect of IFN. One patient was treated with recombinant alpha c-IFN. After 2 months there was a dramatic reduction in the number of HCs in the peripheral blood coincident with the loss of the protection effect of IFN against NK lysis of the patient's HCs. NK activity against autologous tumor cells correlated poorly with that against the K562 cell line. We conclude that there is a discordant effect of IFN and IL-2 on NK activity and HC sensitivity to lysis. The Tac receptor appears to play a role in this sensitivity. Caution should be exercised in extrapolating the effects of NK activity against K562 cells to those on HC targets.

Phase II Trial of Autologous Tumor Vaccination, Anti-CD3-Activated Vaccine-Primed Lymphocytes, and Interleukin-2 in Stage IV Renal Cell Cancer

2003 ◽  
Vol 21 (5) ◽  
pp. 884-890 ◽  
Author(s):  
Alfred E. Chang ◽  
Qiao Li ◽  
Guihua Jiang ◽  
Donna M. Sayre ◽  
Thomas M. Braun ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Lymph Nodes ◽  
Tumor Cells ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cell Cancer ◽  
Interleukin 2 ◽  
Stage Iv ◽  
Autologous Tumor ◽  
Cytokine Release

Purpose: Previous preclinical and clinical studies have demonstrated that autologous tumor vaccines can induce relatively specific tumor-reactive T cells in draining lymph nodes. The adoptive transfer of these cells can result in tumor regression. Patients and Methods: Patients with stage IV renal cell cancer (RCC) were vaccinated with irradiated autologous tumor cells admixed with Calmette-Guérin bacillus. Approximately 7 days later, vaccine-primed lymph nodes (VPLNs) were harvested and the lymphoid cells secondarily activated with anti-CD3 monoclonal antibody and expanded in interleukin 2 (IL-2). The activated cells were subsequently infused intravenously along with the concomitant administration of bolus IL-2 (360,000 U/kg intravenously × 15 doses). Results: Thirty-nine patients were entered onto the study, of whom 34 completed an initial course of cell therapy consisting of a mean (SEM) number of 4.3 (2.2) × 1010 VPLN cells. Among subjects who received cell therapy, there were nine responses (four complete responses [CRs] and five partial responses [PRs]), for an overall response rate of 27%. The durations of the CRs were > 48, 45, > 35, and 12 months, and the durations of the PRs were > 63, 48, 15, 12, and 4 months. Cultured tumor cells were available to assess in vitro cytokine release of VPLN cells in 24 subjects. The median cytokine release ratio of interferon gamma (IFNγ) to IL-10 for responders and nonresponders was 992 and 5, respectively, which was significantly different (P = .047). Conclusion: The treatment protocol resulted in durable tumor responses in patients with advanced RCC. The ratio of IFNγ and IL-10 cytokines released in response to tumor by the VPLN cells was a significant correlate with tumor response.

Generation of cytotoxic immune responses during the progression of a rat glioma

1994 ◽  
Vol 80 (1) ◽  
pp. 90-96 ◽  
Author(s):  
Frank P. Holladay ◽  
Rajani Choudhuri ◽  
Teresa Heitz ◽  
Gary W. Wood
Keyword(s):  
Immune Responses ◽  
Tumor Progression ◽  
Tumor Cells ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Interleukin 2 ◽  
Autologous Tumor ◽  
Content Type ◽  
Tumor Associated Antigens

✓ Cytotoxic T lymphocytes specific for tumor-associated antigens are produced by exposing animals to tumor cells and stimulating lymphocytes from animals immunized in vitro with tumor cells and small amounts of interleukin-2 (IL-2). This study was designed to determine whether a fast-growing immunogenic avian sarcoma virus-induced glioma produces primed cytotoxic T lymphocyte precursors during its progression. Lymphocytes from intracerebral glioma-bearing rats generally failed to proliferate in vitro in response to immunization with tumor cells and IL-2 and, when proliferative responses were observed, the lymphocytes were not cytotoxic for glioma cells. However, when the same tumor was growing subcutaneously, lymphocytes proliferated and exhibited glioma-specific cytotoxicity when stimulated in vitro with autologous tumor cells and IL-2. Subcutaneous immunization of intracerebral glioma-bearing rats with tumor cells and adjuvant induced strong cytotoxic T lymphocyte responses. The results demonstrated that, while intracerebral tumor progression itself does not induce an antiglioma immune response, immune responses to tumor-associated antigens may be induced by systemic immunization of tumor-bearing animals. The results suggest that the immunogenicity of brain tumors is masked by the immunologically privileged status of the brain, not by the induction of generalized immune suppression during tumor progression.

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