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

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 × 10(9) 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.

Zoledronate-activated Vγ9γδ T cell-based immunotherapy is feasible and restores the impairment of γδ T cells in patients with solid tumors.

Gamma/delta (γδ) T cells play a role in innate immunity and exhibit cytotoxicity toward a large range of tumor types. Recent studies have shown that aminobisphosphonates may be applied to a culture in which a large number of γδ T cells are proliferated ex vivo. We carried out a clinical study of 25 patients with various solid tumors to determine further the safety, immunologic effect and feasibility of zoledronate-activated Vγ9γδ T cell-based immunotherapy. No severe toxicity was observed. In the cells used for the first treatment, the total cell number, frequency and number of CD3(+) Vγ9(+) γδ T cells were 409 ± 284 × 10(7) cells, 56 ± 33% and 255 ± 242 × 10(7) cells, respectively. Aminobisphosphonate therapy or chemotherapy resulted in the suppression of CD3(+) Vγ9(+) γδ T-cell proliferation. The numbers of CD3(+) T cells, CD3(+) Vγ9(+) γδ T cells and CD27(-) CD45RA(-) Vγ9(+) subsets in peripheral blood were significantly lower in patients than in healthy subjects (P < 0.05). From such an impaired immunologic condition, the numbers and frequencies of CD3(+) Vγ9(+) γδ T cells and CD27(-) CD45RA(-) subsets significantly increased in patients treated with this immunotherapy. Zoledronate-activated Vγ9γδ T cell-based immunotherapy that restores the number of Vγ9γδ T cells in cancer patients may provide another mode of adoptive immunotherapy.

A case of recurrent ovarian cancer successfully treated with adoptive immunotherapy and lentinan.

BACKGROUND: Immunotherapy is useful for the prevention of the post-operative recurrence of some types of cancer and, in combination with certain anticancer drugs, is expected to prolong survival time. However, the clinical efficacy of immunotherapy alone against advanced cancer has not yet been demonstrated. CASE REPORT: A 67-year-old woman with ovarian cancer who had undergone post-operative adjuvant chemotherapy suffered from recurrent cancer in the lymph nodes. A partial response to adoptive immunotherapy and the administration of the biological response modifier, lentinan containing beta-glucan as the principal component, was maintained for five months without the use of chemotherapy. CONCLUSION: Adoptive immunotherapy with lentinan alone was potentially useful for the treatment of lymph node metastases from ovarian cancer.

Efficacy of immuno-cell therapy in patients with advanced pancreatic cancer.

BACKGROUND: Patients with advanced pancreatic carcinoma have a risk of relapse after primary therapy, and the prognosis for these patients remains bleak. The effect of immuno-cell therapy in advanced pancreatic carcinoma, with or without other standard therapies, was examined. PATIENTS AND METHODS: Forty-six patients with advanced pancreatic carcinoma, undergoing immuno-cell treatment, were evaluated. RESULTS: Of all the patients, those who received immuno-cell therapy alone accounted for 15.4% of partial response (PR), 23.1% of long-term stable disease (SD), 46.2% of SD and 15.4% of progressive disease (PD), and had a 50% survival time of 14.5 months. The respective values for the 28 patients undergoing immuno-cell therapy with gemcitabine were 10.7% of PR, 10.7% of long-term SD, 32.1% of SD and 46.4% of PD, with a 50% survival time of 15.8 months; for 5 patients undergoing immuno-cell therapy with UFT or TS-1, the values were 0% of PR, 0% of SD, 20.0% of SD and 80.0% of PD, with a 50% survival time of 16.1 months. CONCLUSION: The combination of immuno-cell therapies with standard therapies may be effective in the short-term in patients with advanced pancreatic cancer. Long-term survival depends on the presence of metastases and the duration of coadministration with these standard therapies.

[Favorable response obtained by low dose chemotherapy in an elderly patient with extensive small cell lung cancer and renal dysfunction].

An 82-year-old man with extensive small cell lung cancer was treated with 2 courses of low dose CPT-11 (40 mg/body, day 1, 8 and 15) and carboplatin (100 mg/body, day 1). The reduction in tumor sizes evaluated by two-direction measurement was 88%. His creatinine clearance rates before and after chemotherapy were 20 and 28 ml/min, respectively. Temporary leukopenia (900/microl) during the second course of chemotherapy was quickly reversed by the administration of G-CSF, without any episode of infection. Low dose CPT-11 and carboplatin seems to be a promising regimen for elderly patients with small cell lung cancer and renal dysfunction. Cancer tends to increase in old age groups. We consider that it is necessary to examine ideal low dose chemotherapies that can be effective yet preserve quality of life.

[Epidural, mediastinal and subcutaneous emphysema in a patient with suspected torme fruste of Marfan syndrome].

A 17 year-old youth presented with swelling of both sides of neck after a fight with a friend. He had been sick with an upper respiratory tract infection for a few days with frequent coughing. Chest radiography showed subcutaneous and mediastinal emphysema. Neck CT at the level of C7 showed air around the trachea, extending to the subcutaneous tissue and the epidural space through the intervertebral foramen. His height was 180 cm and his weight 55 kg, and he had a 181 cm arm span. He had scoliosis and arachnodactyly, and ultrasonic cardiography demonstrated mitral and tricuspid regurgitation. These findings agreed partially with the clinical criteria of Marfan syndrome. Thus, forme fruste of Marfan syndrome was suspected. A rapid rise of airway pressure induced by a coughing attack and loud shouting during the fight probably caused the laceration of the connective tissue in the airway, resulting in mediastinal and epidural emphysema. In this case report, CT at the C7 level satisfactorily identified air in the mediastinum extending to the epidural space through intervertebral foramen.