Factors associated with non-completion of palliative radiotherapy for spinal metastasis in patients with terminal cancer: a retrospective study.

BACKGROUND: Predictors of non-completion of radiotherapy (RT) should be identified to determine the optimal RT dose. Therefore, this study aimed to explore factors associated with non-completion of palliative RT in patients with terminal cancer. METHODS: In this retrospective study, patients with terminal cancer who received RT (not including single-fraction RT) for relief of pain caused by spinal metastasis were categorized into complete and incomplete groups. Baseline characteristics, hematologic test data [e.g., total lymphocyte count (TLC)], performance status, palliative performance scale (PPS) score, psoas muscle index (PMI), Charlson comorbidity index, and age-adjusted Charlson comorbidity index of the patients were compared between the two groups. RESULTS: The complete group comprised 58 patients (median age: 68 years; female/male: 17/41; number of irradiation fractions: ≥2 to <10, 20 patients; 10, 34 patients; and >10, 4 patients), and the incomplete group comprised 9 patients (median age: 68 years; female/male: 3/6; number of irradiation fractions: ≥2 to <10, 2 patients; 10, 7 patients; and >10, 0 patient). The proportion of patient death within 1 week or 1 month was higher in the incomplete group than in the complete group. Compared with that in the incomplete group, TLC measured 1 week before RT (pre-TLC) and PMI recorded before RT were significantly higher in the complete group (P=0.013 and P=0.012, respectively). In multivariable analyses, pre-TLC was significantly associated with the incomplete group (P=0.048). Compared with the complete group, the incomplete group included several patients whose PPS scores rapidly decreased. CONCLUSIONS: Pre-TLC can predict non-completion of palliative RT in patients with terminal cancer.

Spinal Instability as a Prognostic Factor in Patients With Spinal Metastasis of Castration-resistant Prostate Cancer.

BACKGROUND/AIM: To evaluate the Spinal Instability Neoplastic Score (SINS) for prediction of survival in patients with spinal column metastasis of castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS: A retrospective study of spinal instability was performed in patients with CRPC using SINS. Overall survival was evaluated starting from the time of SINS evaluation. The subjects were 42 patients with CRPC among 261 cases diagnosed with metastatic spinal tumors by radiologists, among 42,152 cases that underwent a body computed tomography scan at Kawasaki Medical School Hospital within 32 months from December 2013 to July 2016. RESULTS: The median age was 78 (range=55-91 years), the median prostate-specific antigen (PSA) level at SINS evaluation was 42.1 (0.1-3,121.6) ng/ml, and 11 patients had visceral metastasis. The median periods from diagnosis of bone metastasis and development of CRPC to SINS evaluation were 17 (0-158) and 20 (0-149) months, respectively. The spine was stable in 32 cases (group S) and potentially unstable or unstable in 10 (24%) (group U). The median observation period was 17.5 (0-83) months and 36 patients died. The median survival period after SINS evaluation was longer in group S than that in group U (20 vs. 10 months, p=0.0221). In multivariate analysis, PSA level, visceral metastasis, and spinal instability were significant prognostic factors. The hazard ratio for patients in group U was 2.60 (95%CI=1.07-5.93, p=0.0345). CONCLUSION: Spinal stability evaluated using SINS is a new prognostic factor for survival of patients with spinal metastasis of CRPC.

Neutrophil­to­lymphocyte ratio before each chemotherapy line predicts clinical outcomes in patients with unresectable gastric cancer.

The neutrophil-to-lymphocyte ratio (NLR) is a well-known prognostic biomarker for patients with gastric cancer (GC). However, for patients with GC treated with palliative chemotherapy, the predictive values of NLR remain obscure. Therefore, the present study evaluated the clinical impact of NLR in patients with GC treated with a series of chemotherapies. The present study retrospectively evaluated 83 patients with unresectable GC who received a series of chemotherapies. NLR in the blood was calculated before each chemotherapy initiation (before 1st-, 2nd- and 3rd-line treatment). Of the 83 patients enrolled, 56 patients (67%) received 2nd-line chemotherapy and 34 patients (41%) received 3rd-line chemotherapy. NLR at 1st-line ranged from 0.72 to 48.9 (median NLR, 3.00). Therefore, the median NLR of 3.00 was used as a definite cut-off value throughout the present study. All patients were dichotomized into NLR-high (>3.00) and NLR-low group (<3.00) by NLR evaluated before each line of chemotherapy. The median overall survival (OS) time of the low-NLR group was better than that of the high-NLR group from 1st-line to 3rd-line treatment (1st-line: 18.1 vs. 8.0 months, P=0.06; 2nd-line: 10.7 vs. 4.5 months, P=0.0001; 3rd-line: 8.7 vs. 4.7 months, P=0.003). Of the 24 patients treated with 3rd-line nivolumab, patients with low NLR exhibited better OS than those with high NLR (8.3 months in low-NLR and 6.6 months in high-NLR, P=0.06). In conclusion, NLR should be performed before each chemotherapy line in the clinical setting and may predict outcomes in patients with unresectable GC, including those treated with nivolumab.

Republication: A Prospective Observational Study of Adoptive Immunotherapy for Cancer Using Zoledronate-Activated Killer (ZAK) Cells - An Analysis for Patients With Incurable Pancreatic Cancer.

BACKGROUND/AIM: Adoptive immunotherapy (AIT) using autologous zoledronate-activated killer (ZAK) cells has been performed for developing a novel modality of cancer treatment. In this study, data series from incurable pancreatic cancer were analyzed. PATIENTS AND METHODS: Patients were treated with AIT using intravenous administration of ZAK cells every 3 to 4 weeks in combination with standard chemotherapy and possible clinical benefits were examined. RESULTS: Seventy-five patients were treated. A median overall survival (OS) time of 6.7 months was achieved for all patients and 13.1 months for those treated 5 times or more, that increased to 14.6 and 18.3 months, respectively, when the previous treatment period of chemotherapy alone was included in the analysis. The disease control rate was 58.5 %. Multivariate regression analysis showed a significant positive correlation between the survival and baseline value of lymphocyte percentage in white blood cell counts (p=0.031). CONCLUSION: The data suggest that AIT using ZAK cells in combination with chemotherapy is safe and feasible and may be effective in prolonging survival for patients with incurable pancreatic cancer. The lymphocyte percentage at baseline may be a good biomarker for predicting the survival benefit of ZAK cell AIT.

Erratum: Adoptive immunotherapy for gastric cancer using zoledronate-activated killer cells: A prospective observational study.

[This corrects the article DOI: 10.3892/mco.2020.2125.].

Concordance of acquired mutations between metastatic lesions and liquid biopsy in metastatic colorectal cancer.

AIM: To evaluate whether PCR-reverse sequence-specific oligonucleotide can examine the concordance between liquid biopsy and metastatic lesions with acquired resistance. MATERIALS & METHODS: We examined acquired mutations in chemoresistant lesions and blood obtained from four patients with RAS wild-type metastatic colorectal cancer who underwent treatment with anti-epidermal growth factor receptor antibodies. RESULTS: In one patient, metastatic lesions harbored diverse acquired mutations in KRAS in all seven metastases; the two acquired mutations were detectable in blood collected after the patient acquired resistance. None of the other patients exhibited liquid biopsy mutations, except one, with a BRAF mutation confirmed in primary tumor and peritoneal dissemination. CONCLUSION: Liquid biopsy based on PCR-reverse sequence-specific oligonucleotide is a successful procedure for capturing acquired mutations with precise information on the RAS mutational spectrum.

Clinical and epigenetic features of colorectal cancer patients with somatic POLE proofreading mutations.

BACKGROUND: Mutations in the POLE gene result in an ultra-hypermutated phenotype in colorectal cancer (CRC); however, the molecular characterisation of epigenetic alterations remains unclear. We examined the genetic and epigenetic profiles of POLE-mutant CRC to elucidate the clinicopathological features of the associated genetic and epigenetic alterations. RESULTS: Tumour tissues (1,013) obtained from a cohort of patients with CRC were analysed to determine associations between the proofreading domain mutations of POLE with various clinicopathological variables, microsatellite instability (MSI) status, BRAF and KRAS mutations, and the methylation status of key regions of MLH1, MGMT, and SFRP2 promoters by calculating the methylation scores (range 0-6). Only four cases (0.4%) exhibited pathogenic POLE hotspot mutations (two p.P286R [c.857C > G], one p.V411L [c.1231G > C], and p.S459F [c.1376C > T] each), which were mutually exclusive to BRAF and KRAS mutations and MSI. CRC patients were divided into four subgroups: patients with POLE mutations (POLE, 0.4%, n = 4), patients with both MSI and extensive methylation in MLH1 (MSI-M, 2.9%, n = 29), patients with MSI but no extensive methylation in MLH1 (MSI-U, 3.6%, n = 36), and patients without MSI (non-MSI, 93.2%, n = 944). The POLE group was younger at diagnosis (median 52 years, P < 0.0001), with frequent right-sided tumour localisation (frequency of tumours located in the right colon was 100%, 93.1%, 36.1%, and 29.9% in POLE, MSI-M, MSI-U, and non-MSI, respectively; P < 0.0001), and was diagnosed at an earlier stage (frequency of stages I-II was 100%, 72.4%, 77.8%, and 46.6% in POLE, MSI-M, MSI-U, and non-MSI, respectively, P < 0.0001). The mean methylation score in POLE was not different from that in MSI-U and non-MSI, but the methylation signature was distinct from that of the other subgroups. Additionally, although the examined number of POLE-mutant tumours was small, the number of CD8-positive cells increased in tumours with partial methylation in the MLH1 gene. CONCLUSIONS: CRC patients with POLE proofreading mutations are rare. Such mutations are observed in younger individuals, and tumours are primarily located in the right colon. Diagnosis occurs at an earlier stage, and distinct epigenetic alterations may be associated with CD8 cell infiltration.

Adoptive immunotherapy for gastric cancer using zoledronate-activated killer cells: A prospective observational study.

For several years, adoptive immunotherapy (AIT) has been performed using autologous zoledronate-activated killer (ZAK) cells to develop a novel modality for cancer treatment. In the current study, data from 50 patients with incurable gastric cancer were analyzed. Patients were treated with AIT using intravenous ZAK cells every 3-4 weeks in combination with chemotherapy of the physician's choice. The possible clinical benefits were subsequently examined. The median overall survival (OS) time of all patients was 7.5 months. In patients that received 5 or more rounds of treatment, the OS was 13.5 months. Additionally, the OS times of 1st, 2nd or later line chemotherapy with ZAK cell AIT were 27.3 months and 13.3 months, respectively. No objective response was observed and the disease control rate was 67.9%. No severe adverse event was recorded. Functional Assessment of Cancer Therapy-Biologic Response Modifier analysis revealed possible improvement of quality of life after ZAK cell AIT. Univariate analysis revealed a significant positive association between longer survival times and baseline lymphocyte percentages in white blood cell counts (P<0.001), serum albumin (P=0.001), C-reactive protein (P=0.006), carbohydrate antigen (CA)19-9 (P=0.010), neutrophil-lymphocyte ratio (P<0.001) and Glasgow prognostic score (GPS). Only the GPS value (P=0.024) was a significant survival marker when analyzed using the multivariate Cox proportional hazards model. Although the results cannot provide a definitive conclusion, the current suggested that ZAK cell AIT in combination with chemotherapy is safe, feasible and may be a promising treatment option for patients with incurable gastric cancer. The GPS value at baseline may be a potential biomarker for chemo-immunotherapy.

[The Liaison Service Models of Care for Metastatic Spinal Tumor].

Advances in cancer treatment helped in increasing the life expectancy of patients with cancer. However, a concomitant increase in the number of patients with bone metastases can be expected. A new multidisciplinary treatment strategy for patients with metastatic spinal tumors was designed, and has been practiced from 2013 in our hospital. The benefits of liaison treatment for metastatic spinal tumors is useful for early detection and early treatment before the collapse of the stabilization mechanism and the appearance of neurological symptoms, and enables team medical care by various experts. This system is a useful treatment for metastatic spinal tumors, because it enables radiotherapy and/or surgery before the onset of skeletal related events(SRE)and will also help maintain the activities of daily living(ADL)and quality of life(QOL)for patients with metastatic spinal tumors.

[Incidence of Catheter-Related Thrombosis in Patients with Long-Term Indwelling Central Venous Port Who Received Chemotherapies for Unresectable Advanced Digestive Cancers].

BACKGROUND: Most patients with unresectable advanced digestive cancers require placement of a fully implantable venous access port to facilitate safe delivery of anti-cancer drugs. Anti-VEGF therapies are commonly used even though they increase the risk of thrombosis. The objective of this study was to assess the incidence of radiologically confirmed catheter-related thrombosis(CRT)in patients with advanced digestive cancers. METHODS: We retrospectively reviewed 88 patients with advanced digestive cancers who had adapted implantable ports placed in our institution for chemotherapy. RESULTS: Thirty-nine patients were diagnosed with colorectal cancer, 26 with gastric cancer, 12 with pancreatic cancer, 8 with esophageal cancer, and 3 with other cancers. During follow-up, 22 patients(25%)received anti-VEGF therapies, while 66 patients(75%)did not. Four out of 88 patients(4.5%)had asymptomatic CRT. The incidence of CRT was the same(4.5%)regardless of whether the patient received anti-VEGF therapy. CONCLUSIONS: In patients with digestive cancers who had implantable venous access ports, the incidence of the CRT was 4.5% with no association with anti-VEGF therapies.

[Introduction].

Time has come when oncology has met immunology. Immune checkpoint inhibitors(ICIs)are being approved as standard cancer treatments, day by day. ICIs, however, have serious immune-related adverse events(irAEs)in a diverse manner, requiring the establishment of team-approach system to manage irAEs. Here, irAEs are summarized and their managements are discussed.

A Prospective Observational Study of Adoptive Immunotherapy for Cancer Using Zoledronate-Activated Killer (ZAK) Cells - An Analysis for Patients with Incurable Pancreatic Cancer.

BACKGROUND/AIM: Adoptive immunotherapy (AIT) using autologous zoledronate-activated killer (ZAK) cells has been performed for developing a novel modality of cancer treatment. In this study, data series from incurable pancreatic cancer were analyzed. PATIENTS AND METHODS: Patients were treated with AIT using intravenous administration of ZAK cells every 3 to 4 weeks in combination with standard chemotherapy and possible clinical benefits were examined. RESULTS: Seventy-five patients were treated. A median overall survival (OS) time of 6.7 months was achieved for all patients and 13.1 months for those treated 5 times or more, that increased to 14.6 and 18.3 months, respectively, when the previous treatment period of chemotherapy alone was included in the analysis. The disease control rate was 58.5 %. Multivariate regression analysis showed a significant positive correlation between the survival and baseline value of lymphocyte percentage in white blood cell counts (p=0.031). CONCLUSION: The data suggest that AIT using ZAK cells in combination with chemotherapy is safe and feasible and may be effective in prolonging survival for patients with incurable pancreatic cancer. The lymphocyte percentage at baseline may be a good biomarker for predicting the survival benefit of ZAK cell AIT.

[Current Cancer Immunotherapy Using Activated Lymphocytes - Do Lymphocytes Actually Recognize Cancer Cells ?].

Molecular cloning of interleukin-2(IL-2)has enabled adoptive cell therapy(ACT)to be established by using autologous activated lymphocytes. The low of regenerative medicine will promote the active development of ACT for public use, and ACTs that utilize tumor-infiltrating lymphocytes(TIL), in vitro tumor-sensitized lymphocytes, natural killer T cells, and gammadelta T cells are being evaluated as advanced medical treatments in Japan. In addition, chimeric antigen receptor genemodified T(CAR-T)cells and T cell receptor gene-modified T(TCR-T)cells are available for investigational clinical use. CART and TCR-T cells have been associated with serious adverse events as well as drastic clinical efficacies, indicating the importance of choosing the antigens to be targeted. Presently, it is accurate to state that lymphocytes do recognize cancer cells. Clinical ACT research focusing on TIL and mutated cancer antigens will be initiated for the development of personalized immunotherapy for cancer in the future.

Imatinib plasma levels during successful long-term treatment of metastatic-gastrointestinal stromal tumors.

BACKGROUND/AIMS: To investigate whether imatinib dosage correlated with effective plasma levels and clinical characteristics for Japanese patients undergoing long-term (≥2 years) imatinib therapy for GISTs. METHODOLOGY: Twenty-five patients who received imatinib for a metastatic pathologically diagnosed GISTs at our hospital were enrolled. Imatinib response was assessed according to Choi's criteria. Blood samples were collected 22­26 h after the previous imatinib dose before the next scheduled dose. Results: Fourteen patients were male and the median age was 65 years. The median duration of imatinib therapy was 3.8 years (range, 2.0­11.5 years). The median plasma level of imatinib was 1098 ng/ml and the minimal plasma level after ≥5 years of therapy was 789 ng/ml. Imatinib dosage was significantly correlated with history of gastrectomy. The minimum body surface area of patients who received 400-mg/day imatinib dosage was 1.560 m2. CONCLUSIONS: The minimum level in all patients showing response for ≥5 years of treatment was 789 ng/ml, suggesting an effective plasma imatinib level of ≥800 ng/ml. Our results suggest that imatinib dosage of 400 mg/day is recommended for a patient with a large BSA (≥1.56 m2) and that of 300 mg/day might be sufficient for patients who have undergone a gastrectomy.

A case of stroke due to tumor emboli associated with metastatic cardiac liposarcoma.

Cardioembolic stroke due to tumor emboli is a rare complication of neoplasm. A patient with metastatic cardiac liposarcoma who suffered from embolic stroke is reported. Autopsy confirmed that the cardiac tumor was a metastatic liposarcoma from the retroperitoneum, and the cerebral vessel was occluded by tumor cells and fibrin clot.

Targeting of CD4+CD25high cells while preserving CD4+CD25low cells with low-dose chimeric anti-CD25 antibody in adoptive immunotherapy of cancer.

The CD4+CD25high regulatory T (Treg) cells have been demonstrated to negatively modulate anti-tumor immune responses in cancer patients. In this study, effects of low dose anti-CD25 antibody (Ab) to attenuate Treg cells were investigated in cancer patients in vitro and in vivo. Peripheral blood mononuclear cells (PBMCs) from cancer patients were cultivated in vitro in the presence of a high-affinity chimeric anti-CD25 Ab (basiliximab). The CD4+CD25high population, interferon-gamma (IFN-gamma) production and FOXP3 expression were analyzed using flow cytometry (FCM), enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, respectively. During in vivo studies, basiliximab was administered intravenously on day 1, followed by AIT using autologous activated lymphocytes on day 8, and the treatment cycle was repeated. Subjective and objective effects were observed, and patients' PBMCs were subjected to FCM and RT-PCR analysis. In vitro analysis revealed that a low concentration of 0.01 microg/ml basiliximab reduced almost all of CD4+CD25high cells, but less of the CD4+ CD25low cells, and augmented IFN-gamma production of activated PBMCs. FOXP3 mRNA expression of PBMCs was not affected with or without basiliximab. An in vivo study of 9 metastatic cancer patients (7 colorectal and 2 esophageal) demonstrated no subjective or objective adverse effects, even under repeated administration of basiliximab. The results suggested that low-dose basiliximab can safely be administered repeatedly, and can target CD4+CD25high Treg cells whilst relatively preserving CD4+CD25low activated T cells. The host conditioning with low-dose basiliximab may augment the efficacy of AIT for cancer using activated autologous lymphocytes.

[A resected case of postoperative liver metastasis of a gastrointestinal stromal tumor showing complete response after imatinib treatment].

A 71-year-old man visited the hospital complaining of nausea in December 2002. Following a diagnosis of a gastrointestinal stromal tumor (GIST), partial resection of the stomach was performed in January 2003. The tumor was immunohistochemically positive for c-kit and CD34. The tumor size was 6.5 x 5.0 x 4.5 cm with a mitotic index of 25 out of 50 in the high-power field. The pathological diagnosis indicated a high-risk GIST. Treatment with imatinib at a dose of 400 mg/day was started because of liver metastasis of the GIST in January 2004. The liver metastasis was gradually reduced and exhibited cystic change. We considered that there was a complete response without accumulation by FDG-PET in June 2007. An hepatic segmentectomy was performed and imatinib was discontinued in July 2007. Most intratumorale in the specimen underwent hyaline degeneration after pathological examination, but there were viable cells in a portion of the tumor border. Imatinib treatment was resumed because of recurrence in the remnant stomach four months postoperatively owing to imatinib withdrawal. In making a diagnosis at the cell level by FDG-PET, it was difficult to determine the effectiveness of imatinib, and therefore, it is suggested that imatinib treatment must be continued after surgical resection.

Dose-finding study of anti-CD25 antibody for targeting regulatory T cells in locoregional immunotherapy of malignant effusion.

Effects of low-dose anti-CD25 antibody on targeting regulatory T (Treg) cells in vitro and in vivo were investigated. Human-mouse chimeric anti-CD25 monoclonal antibody basiliximab was administered into the effusion cavity, followed by locoregional immunotherapy using OK-432 on day 7. Peripheral blood mononuclear cells and effusion lymphocytes (ELs) were collected before and after the basiliximab administration and subjected to further investigations. Surface phenotypes, IFN-gamma production, cytotoxic activity and foxp3 expression of ELs were assessed by flow cytometry, ELISA, 51Cr-releasing assay, and RT-PCR analysis, respectively. We observed that a low concentration of 0.01 microg/ml basiliximab effectively targeted CD4+CD25(bri) Treg cells while preserving CD4+CD25(dim) activated T cells in vitro. This concentration of basiliximab significantly augmented interferon (IFN)-gamma production of ELs when interleukin (IL)-2 was added on day 0 or on day 1 after basiliximab. In the clinical study, intracavitary administration of basiliximab on day 0 followed by OK-432 on day 7 was as safe, well-tolerated, and effective as using OK-432 alone, and a low-dose of 0.002-0.005 mg/kg basiliximab could target CD4+CD25(bri) cells for at least 3 days while relatively preserving CD4+CD25(dim) cells. Foxp3 expression of ELs was not changed definitely by the intracavitary basiliximab. These results suggest that low-dose basiliximab can target Treg cells in vitro and in vivo, and subsequently augment the activation of ELs. Locoregional immunotherapy of malignant effusion using the Treg cell-conditioning regimen with low-dose basiliximab followed by OK-432 administration on day 0 or on day 1 should be evaluated for clinical efficacy in the next phase II trial.

Essential requirement of toll-like receptor 4 expression on CD11c+ cells for locoregional immunotherapy of malignant ascites using a streptococcal preparation OK-432.

Toll-like receptors (TLRs) are important molecules that stimulate the innate immunity in order to eradicate microbial pathogens, after which the adaptive immunity emerges. The involvement of TLRs in the action mechanism of OK-432, a bacterial preparation, was investigated in the locoregional treatment of malignant ascites from gastric cancer. The expression of TLRs in ascites cells was analyzed using reverse-transcription polymerase chain reaction specific for TLRs and by flow cytometry using anti-TLR2, -TLR4, -CD4, -CD8, and -CD11c antibodies. These measurements were compared with the locoregional response of OK-432 immunotherapy for malignant ascites, as well as TNF-alpha producing potential, which was measured by ELISA, of ascites cells stimulated in vitro with OK-432. It was observed that OK-432 immunotherapy for malignant ascites showed 8 positive (67%) and 4 negative responses with the tolerable adverse effects of fever elevation and abdominal pain. The TNF-alpha production of ascites cells by in vitro OK-432 stimulation was significantly higher in responder patients than in non-responders. The clinical responses were correlated with the expression of the TLR4 gene of ascites cells. The TNF-alpha-producing potential of ascites cells by in vitro OK-432 stimulation was dependent on the existence of a CD11c + TLR-4+ cell population in ascites cells. OK-432 was highly stimulatory for TNF-alpha production of ascites cells compared with other biological response modifiers of PSK and LEM. These results suggest that TLR-4 expression on ascites cells of a macrophage lineage is essential for ascites cells to produce TNF-alpha in relation to OK-432 stimulation and for subsequent positive clinical responses in locoregional immunotherapy using OK-432 for malignant ascites from gastric cancer.

Adoptive immunotherapy using autologous lymphocytes sensitized with HLA class I-matched allogeneic tumor cells.

A 29-year-old female breast cancer patient with multiple bone metastases (HLA-A2) was treated with adoptive transfer using autologous peripheral blood mononuclear cells (PBMCs) activated with the HLA-A2-matched allogeneic GC022588 gastric cancer cell line and interleukin-2 plus an immobilized anti-CD3 antibody culture system. The relief of bone pain in parallel with a decrease of serum carcinoembryonic antigen levels was obtained just after the administration of GC022588-activated effector lymphocytes, and a good quality of life was accomplished for 4 months. The GC022588-activated effector lymphocytes included 44% CD4+, 77% CD8+, and 26% CD4+CD8+ phenotypes, and expressed 25% killing activity against GC022588 stimulator cells at an E/T ratio of 50:1. T cell receptor (TCR) usage analysis for the effector cells showed oligoclonal expression of TCRVbeta1, 3, 9, and 11, especially TCRVbeta5.2, 12, 13.1 and 17, and their killing activity was significantly inhibited in the presence of anti-TCRalphabeta antibody and anti-TCRVbeta12 antibody. SSCP analysis revealed clonotypic bands of TCRVbeta12. These results suggest that shared antigens exist between breast and gastric adenocarcinomas. Allogeneic tumor cells can stimulate PBMCs to generate effector cells with selected TCRCDR3 usages that recognize tumor antigens. These effector lymphocytes may be good candidates for the adoptive immunotherapy of cancer.