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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 10/2012

Open Access 01-10-2012 | Original article

Extended survival observed in adoptive activated T lymphocyte immunotherapy for advanced lung cancer: results of a multicenter historical cohort study

Authors: Kazuro Iwai, Kenzo Soejima, Shoji Kudoh, Yoshimasa Umezato, Toru Kaneko, Kouji Yoshimori, Hitoshi Tokuda, Tetsuo Yamaguchi, Akira Mizoo, Yasuhiro Setoguchi, Takashi Kamigaki, Katsunada Fujimoto, Shigenori Goto

Published in: Cancer Immunology, Immunotherapy | Issue 10/2012

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Abstract

Purpose

To clarify the long-term effect of immunotherapy, the effect of adoptive activated T lymphocyte immunotherapy on advanced lung cancer was evaluated in terms of survival time. In addition, the performance status of cancer patients under immunotherapy was examined.

Experimental design

Over 5 × 109 alpha–beta T lymphocytes cultured ex vivo with an immobilized anti-CD3 antibody and interleukin-2 were injected intravenously into patients, once every 2 weeks for 3 months or longer. Follow-up of these patients was carried out using clinical records and by telephone interview questionnaire. Patients undergoing immunotherapy in immunotherapy clinics and those undergoing other anticancer therapies without immunotherapy in seven hospitals in Tokyo were enrolled in this study. Data were analyzed by a third-party statistician. Performance status was studied on another series of various cancer patients who underwent immunotherapy.

Results

The overall median survival time of the patients with the best supportive care, which was obtained using Kaplan–Meier’s model, was 5.6 months, and those with immunotherapy alone, chemotherapy alone, and immuno-chemotherapy were 12.5, 15.7, and 20.8 months, respectively. Using Cox’ proportional hazard model, we examined the possible factors on survival time by univariate analysis. Then, the patients were stratified by gender and histological type for multivariate analysis. Significantly low hazard ratios were observed for immunotherapy and radiotherapy in males with squamous cancer; for chemotherapy and radiotherapy in male with adenocarcinoma; and for immunotherapy in females with adenocarcinoma. Addition of immunotherapy to chemotherapy resulted in a statistically significant decrease in hazard ratio in females with adenocarcinoma. Studies on the performance status (PS), determined according to the European Cooperative Oncology Group criteria, revealed a continuous high level of PS under immunotherapy until around 2 months before death, in contrast to the gradual increase of tumor marker level.

Conclusions

The effectiveness of immunotherapy on advanced lung cancer is limited but may extend life span under certain conditions. Immunotherapy itself provided no clinical benefit by itself as compared with chemotherapy, but a significant additive effect of immunotherapy on chemotherapy was observed in females with adenocarcinoma. Moreover, immunotherapy can maintain good quality of life of the patients until near the time of death.
Literature
1.
Rosenberg SA (1984) Immunotherapy of cancer by systemic administration of lymphoid cell plus interleukin-2. J Biol Resp Modif 3:501–511
2.
Rosenberg SA, Lotse MT, Muul LM, Vetto JT et al (1986) A new approach to the therapy of cancer based on the systemic administration of autologous lymphokine-activated cells and recombinant interleukin-2. Surgery 100:262–272PubMed
3.
Grim EA, Mazumder A, Zhang H, Rosenberg SA (1982) Lymphnokine-activated killer cell phenomenon. Lysis of natural killer resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes. J Exp Med 155:1823–1841CrossRef
4.
Hefeneider SH, Conlon PJ, Henney CS, Gllis S (1983) In vivo interleukin 2 administration augments the generation of alloreactive cytolytic T lymphocytes and resident killer cells. J Immunol 130:222–227PubMed
5.
Rosenberg SA (1984) Immunotherapy of cancer by systemic administration of lymphoid cells plus interleukin-2. J. Biol Response Modif 3:501–511
6.
Donohue JH, Rosenstein M, Chang AE, Lotze MT, Robb RJ, Rosenberg SA (1984) The systemic administration of purified interleukin 2 enhances the ability of sensitized murine lymphocytes to cure a disseminated syngeneic lymphoma. J Immunol 132:2123–2128PubMed
7.
Mulè JJ, Shu S, Schwartz SL, Rosenberg SA (1984) Adoptive immunotherapy of established pulmonary metastasis with LAK cells and recombinant interleukin-2. Science 28:1487–1489CrossRef
8.
Lafreniere R, Rosenberg SA (1985) Successful immunotherapy of murine experimental hepatic metastases with lymphokine-activated killer cells and recombinant interleukin 2. Cancer Res 45:3735–3741PubMed
9.
Mulè JJ, Yang J, Shu S, Rosenberg SA (1986) The anti-tumor efficacy of lymphokine-activated killer cells and recombinant interleukin 2 in vivo: direct correlation between reduction of established metastasis and cytolytic activity of lymphokine-activated killer cells. J Immuol 136:3899–3909
10.
Ettinghausen SE, Rosenberg SA (1986) Immunotherapy of murine sarcomas using lymphokine activated killer cells: Optimization of the schedule and rout of adminstration of recombinant interleukin-2. Cancer Res 46:2784–2792PubMed
11.
Lee K-e, O’Donnell W, Cockett ATK (1988) Ineffectiveness of adoptive chemoinnumotherapy with lymphokine-activated killer cells, interleukin-2, and cyclophosphamide on palpable intradermal murin bladder cancer. J Biol Response Modif 7:43–53
12.
Yoshimori K (1992) A study to increase the therapeutic effects of adoptive immunotherapy in vivo influence on the generation of lymphokine-activated killer (LAK) cells and therapeutic effects of LAK cells with antitumor drug (cyclophosphamide). Arch Nippon Med Sch 59:418–426
13.
Rosenberg SA, Lotze MT, Muul LM, Chang AE, Avis FP et al (1987) A progress report of the treatment of 157 patients with advanced cancer using lymphokine activated killer cells and interleukin-2 or high dose interleukin-2 alone. N Engl J Med 316:889–897PubMedCrossRef
14.
Rosenberg SA, Lotze MT, Yang JC, Topalian SL, Chang AE et al (1993) Prospective randomized trial of high dose interleukin-2 alone or in conjugation with lymphokine- activated killer cell for treatment of advanced cancer. J Natl Cancer Inst 85:622–632PubMedCrossRef
15.
Rosenberg SA, Yang JC, Restifo NP (2005) Cancer immunotherapy: moving beyond current vaccines. Nat Med 9:909–914
16.
Bringle L, Brown NJ, Lewis CE (2002) The role of tumor-associated macrophages in tumor progression: implications for new anticancer therapies. J Pathol 196:254–265CrossRef
17.
Pollard JW (2004) Tumor-educated macrophages promote tumor progression and metastasis. Nat Rev Cancer 4:71–78PubMedCrossRef
18.
Luo Y, Zhou H, Krueger J, Kaplan C, Lee SH et al (2006) Targeting tumor-associated macrophages as a novel strategy against breast cancer. J Clin Invest 116:2132–2141PubMedCrossRef
19.
Powell DJ, Dudley ME, Hogan KA, Wunderlich JR, Rosenberg SA (2006) Adoptive transfer of vaccine-induced peripheral blood mononuclear cells to patients with metastatic melanoma following lymphodepletion. J Immunol 177:6527–6539PubMed
20.
Sangha R, Butts C (2007) L-BLP25: a peptide vaccine strategy in non-small cell lung cancer. Clin Cancer Res 13:4652–4654CrossRef
21.
Kuemmel A, Single K, Bittinger F, Faldum A, Schmidt LH et al (2009) TA-MUC1 epitope in non-small cell lung cancer. Lung Cancer 63:98–105PubMedCrossRef
22.
Wilhelm M, Kunzman V, Eckstain S, Reimer P, Weissinger F et al (2003) Gamma-delta T cells for immune therapy of patients with lymphoid malignancies. Blood 102:200–206PubMedCrossRef
23.
Liu Z, Eltoum I-EA, Guo B, Beck BH, Cloud GA, Lopez RD (2008) Protective immunosurveillance and therapeutic antitumor activity of gamma-delta T cells demonstrated in a mouse model of prostate cancer. J Immunol 180:6044–6053PubMed
24.
Bennouna J, Bompas E, Neidhardt EM, Rolland F, Philip I et al (2008) Phase-I study of Innacell gamma deltaTM, an autologous cell-therapy product highly enriched in gamma9delta2 T lymphocytes, in combination with IL-2, in patients with metastatic renal cell carcinoma. Cancer Immunol Immunother 57:1599–1609PubMedCrossRef
25.
Abe Y, Muto M, Nixed M, Nakagawa Y, Nicol A et al (2009) Clinical and immunological evaluation of zoledronate-activated Vgamma9-gammadelta T-cell-based immunotherapy for patients with multiple myeloma. Exp Hematol 37:956–968PubMedCrossRef
26.
Kimura H, Yamaguchi Y (1997) A phase III randomized study of interleukin-2 lymphokine-activated killer cell immunotherapy combined with chemotherapy after curative or noncurative resection of primary lung carcinoma. Cancer 80:42–49PubMedCrossRef
27.
Takayama T, Sekine T, Makuuchi M, Yamasaki S, Kosuge T et al (2000) Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomized trial. Lancet 356:802–807PubMedCrossRef
28.
Egawa K (2004) On the safety assurance of cell processing carried out in medical institutions for autologous immune-cell therapy. Hum Cell 17:1–6PubMedCrossRef
29.
Egawa K (2004) Immuno-cell therapy of cancer in Japan (review). Anticancer Res 24:3321–3326PubMed
30.
Goto S, Kaneko T, Miyamoto Y, Eriguchi M, Kato A et al (2005) Combined immunocell therapy using activated lymphocytes and monocyte-derived dendritic cells for malignant melanoma. Anticancer Res 25:3741–3745PubMed
31.
Kaneko T, Goto S, Kato A, Akeyama T, Tomonaga M et al (2005) Efficacy of immune-cell therapy in patients with advanced pancreatic cancer. Anticancer Res 25:3709–3714PubMed
32.
Goto S, Noguchi A, Jinguji H, Takahara M (2006) The therapeutic potential of immune-cell therapy of cancer in combination with aminobisphophonates. Anticancer Res 26:3989–3996PubMed
33.
Hyde L, Wolf J, McCracken S, Yesner R (1970) Natural course of inoperable lung cancer. Chest 64:309–312CrossRef
34.
Woods RL, Williams CJ, Levi J, Page J, Bell D et al (1990) A randomized trial of cisplatin and vindesine versus supportive care only in advanced non-small cell lung cancer. Br J Cancer 61:608–611PubMedCrossRef
35.
Helsing M, Bergman B, Thaning L, Hero U (1998) Quality of life and survival in patients with advanced non-small lung cancer receiving supportive care plus chemotherapy with carboplatin and etoposide or supportive care only. A multicentre randomized phase III trial. Joint Lung Cancer Study Group. Eur J Cancer 37:1036–1044CrossRef
36.
Anderson H, Hopwood P, Stephens RJ, Thatcher N, Cottier B et al (2000) Gemcitabine plus best supportive care (BSC) vs BSC in inoperable non-small cell lung cancer—a randomized trial with quality of life as the primary outcomes. UK NSCLC Gemcitabine Group. Non-Small Cell Lung Caner. Br J Cancer 83:447–453PubMedCrossRef
37.
Spiro SG, Rudd RM, Souhami RL, Brown J, Fairlamb DJ et al (2004) Big Lung Trial participants. Chemotherapy versus supportive care in advanced non-small cell lung cancer: improved survival without detriment to quality of life. Thorax 59:828–836PubMedCrossRef
38.
Thatcher N, Chang A, Parikh P, Rodrigues Pereira R Jr et al (2005) Gefinitib plus supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomized, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet 366:1527–1537PubMedCrossRef
39.
Shepherd FA, Pereria JR, Ciuleanu T, Tan EH, Hirsh V et al (2005) Erlotinib in previously treated non-small-cell lung cancer. New Engl J Med 353:123–132PubMedCrossRef
40.
Keller SM, Vangel MG, Adak S, Wagner H, Schiller JH et al (2002) The influence of gender on survival and tumor recurrence following adjuvant therapy of completely resected stage II and IIIa non-small cell lung cancer. Lung Cancer 37:303–309PubMedCrossRef
41.
Japanese Joint Committee for Lung Cancer Registration (2009) A Japanese lung cancer registry study at 2002. Jpn J Lung Cancer 49:975–987CrossRef
Metadata
Title
Extended survival observed in adoptive activated T lymphocyte immunotherapy for advanced lung cancer: results of a multicenter historical cohort study
Authors
Kazuro Iwai
Kenzo Soejima
Shoji Kudoh
Yoshimasa Umezato
Toru Kaneko
Kouji Yoshimori
Hitoshi Tokuda
Tetsuo Yamaguchi
Akira Mizoo
Yasuhiro Setoguchi
Takashi Kamigaki
Katsunada Fujimoto
Shigenori Goto
Publication date
01-10-2012
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 10/2012
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-012-1226-4

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