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

Abstract

PurposeTo 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 designOver 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.ResultsThe 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.ConclusionsThe 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.

Is the CD4/CD8 Ratio an Effective Indicator for Clinical Estimation of Adoptive Immunotherapy for Cancer Treatment?

“…There is some evidence of an association between immunological ability and PS [7]. The present study showed a statistically significant association between change in the CD4/CD8 ratio before and after one course of adoptive immunotherapy and PS among different groups; the antecedent surgery group showed an important benefit of immunotherapy compared with the non-antecedent surgery group (p = 0.0179).…”

“…Many physicians including Egawa, the founder of Japanese clinical immunotherapy who conducted the first clinical investigation of immunotherapy for cancer on his brother, have suggested that patients can maintain ordinary daily life activities during immunotherapy until close to the end of their life. To clarify this postulation, in the present study we analyzed PS during one course of adoptive activated immunotherapy [7,11,12]. Table 4…”

“…However, the effective response rate according to the complete/partial response outlined in the RECIST criteria was determined to be low, adverse reactions were rarely observed, and patients generally showed a good Eastern Cooperative Oncology Group (ECOG) performance status (PS) during the course of immunotherapy. A recent phase 3 trial using Egawa's modified adoptive immunotherapy in combina-tion with chemotherapy also showed important significant additive effects of immunotherapy compared to chemotherapy alone in lung cancer patients at all clinical stages, as well as a positive effect on quality of life (QOL) until near the time of death in advanced lung cancer patients [7]. To date there have been few reports on the efficacy of immunotherapy using accurate estimation indices [8,9], especially for modified adoptive immunotherapy.…”

Nola eragiten du 2-Interleukinak T-zelulen nukleoko proteinen fosforilazio mailan?

“…Jada abian dira immunoterapian oinarritzen diren saio kliniko batzuk, hesteetako hantura [3], gaixotasun autoimmuneak [4-6] edota minbizia [7,8] menderatzea helburu dutenak. Gaixotasunei aurre egiteko estrategia iraultzaile hau, duela hiru hamarkada sortu zen, melanoma pairatzen zuen gaixo bati T-zelulen hazkuntza bultzatzen duen 2-interleukina (IL-2) eman zitzaionean [9,10].…”

Change in peripheral blood lymphocyte count in dogs following adoptive immunotherapy using lymphokine-activated T killer cells combined with palliative tumor resection

“…The therapeutic efficacy of T-LAK therapy is thought to be mediated by the following 2 pathways: (1) cytotoxic activity of T-LAK against tumor cells (Sekine et al, 1993) and (2) activation of anti-tumor immune responses by various cytokines secreted from T-LAK (Kwak et al, 2000;Ishikawa et al, 2011). In human medicine, improvements in the proportions and cytokine production from autologous T lymphocytes have been reported (Hirokawa et al, 2009;Ishikawa et al, 2011;Sun et al, 2011;Noguchi et al, 2014) in addition to clinical effects, such as decreasing postoperative recurrence (Takayama et al, 2000;Xie et al, 2012;Zhong et al, 2012), improving quality of life Iwai et al, 2012), and prolonging survival Iwai et al, 2012;Zhang et al, 2015).…”