Autologous Formalin-fixed Tumor Vaccine Research Articles

A multicenter, randomized, placebo-controlled phase IIb trial of an autologous formalin-fixed tumor vaccine for newly diagnosed glioblastomas.

An autologous formalin-fixed tumor vaccine (AFTV) derived from resected glioblastoma (GBM) tissue can be used against unidentified tumor antigens. Thus, the authors conducted a multicenter double-blind phase IIb trial to investigate the efficacy of an AFTV. Eligible patients were adults with supratentorial GBMs, 16-75 years of age, with Karnofsky Performance Scale (KPS) scores ≥ 60%, and no long-term steroid administration. An AFTV comprising fixed paraffin-embedded tumor tissue with immune adjuvants or an identical placebo without fixed tumor tissue was injected intradermally over three courses before and after chemoradiotherapy. The primary and secondary end points were overall survival (OS), progression-free survival (PFS), and 3-year survival rate. Sixty-three patients were enrolled. The average patient age was 61 years. The median KPS score was 80%, and the median resection rate was 95%. The full analysis set of 57 patients indicated no significant difference in OS (p = 0.64) for the AFTV group (median OS 25.6 months, 3-year OS rate 38%) compared with the placebo group (31.5 months and 41%, respectively) and no difference in PFS (median PFS 13.3 months in both groups, p = 0.98). For patients with imaging-based total tumor removal, the 3-year PFS rate was 81% in the AFTV group versus 46% in the placebo group (p = 0.067), whereas the 3-year OS rate was 80% versus 54% (p = 0.16), respectively. Similar results were obtained in the p53-negative subgroups. Severe adverse effects were not observed. The AFTV may have potential effects in certain patient subgroups. A phase III study for patients with total tumor removal remains warranted to confirm these findings. Clinical trial registration no.: UMIN000010602 (UMIN Clinical Trials Registry).

P53-negative status and gross total resection as predictive factors for autologous tumor vaccine treatment in newly diagnosed glioblastoma patients.

Among primary brain tumors, glioblastoma (GBM) is the most common and aggressive in adults, with limited treatment options. Our previous study showed that autologous formalin-fixed tumor vaccine (AFTV) contributed to prognostic improvements in newly diagnosed GBM patients. However, some patients died early despite the treatment. The discovery of predictive factors in the treatment was warranted for efficient patient recruitment and studies to overcome resistance mechanisms. Identifying prognostic factors will establish AFTV guidelines for patients who may respond to the therapy. Data from 58 patients with newly diagnosed GBM, including 29 who received standard therapy plus AFTV (AFTV group) and 29 who received standard treatment (control group) were analyzed. Several data including patient age, sex, the extent of removal, and various cell immunohistochemistry (IHC) parameters were also included in the analysis. Both univariate and multivariate analyses revealed that gross total resection (GTR) and negative p53 were associated with a better prognosis only in the AFTV group. In the IHC parameters, CD8 staining status was also one of the predictive factors in the univariate analysis. For blood cell-related data, lymphocyte counts of 1100 or more and monocyte counts of 280 or more before chemo-radiotherapy were significant factors for good prognosis in the univariate analysis. A p53-negative status in IHC and GTR were the predictive factors for AFTV treatment in newly diagnosed GBM patients. Microenvironment-targeted treatment and pretreatment blood cell status may be key factors to enhance therapy effects.

Maximum resection and immunotherapy improve glioblastoma patient survival: a retrospective single-institution prognostic analysis

Glioblastoma (GBM) is a refractory disease with a poor prognosis and various methods, including maximum resection and immunotherapy, have been tested to improve outcomes. In this retrospective study we analyzed the prognostic factors of 277 newly diagnosed GBM patients over 11 years of consecutive cases at our institution to evaluate the effect of these methods on prognosis. Various data, including the extent of removal (EOR) and type of adjuvant therapy, were examined and prognostic relationships were analyzed. The median overall survival (OS) of the entire 277-case cohort, 200 non-biopsy cases, and 77 biopsy cases was 16.6 months, 19.7 months, and 9.7 months, respectively. Gross total removal (GTR; 100% of EOR) was achieved in 32.9% of the cases. Univariate analysis revealed younger age, right side, higher Karnofsky performance status, GTR, intraoperative magnetic resonance imaging (MRI) use for removal, proton therapy, combination immunotherapy, and discharge to home as good prognostic factors. Intraoperative MRI use and EOR were closely related. In the multivariate analysis, GTR, proton therapy, and a combination of immunotherapies, including autologous formalin-fixed tumor vaccine, were the significant prognostic factors. A multivariate analysis of 91 GTR cases showed that immunotherapy contributed to prognostic improvements. The median OS and 5-year OS % values were 36.9 months and 43.3% in GTR cases receiving immunotherapy. In conclusion, GTR, proton therapy, and immunotherapy were good prognostic factors in single-center GBM cases. Tumor vaccine therapy for GTR cases achieved a notably high median survival time and long-term survival ratio, indicating its usefulness in GTR cases.

IMT-05 PHASE III RANDOMIZED CLINICAL TRIAL OF AFTV FOR NEWLY DIAGNOSED GLIOBLASTOMA

BACKGROUNDThe highly fatal glioblastoma has an extremely poor prognosis and development of a new treatment is desired. Local treatment is limited due to its high invasiveness, and immunotherapy utilizing self-immune mechanism is theoretically expected. An autologous formalin-fixed tumor vaccine (AFTV) is a vaccine that is prepared using formalin-fixed tumor tissue and recognizes tumor antigen peptides to induce cytotoxic T cells. We have previously conducted three clinical trials using AFTV for patients with newly diagnosed glioblastoma since 2004. The third trial was a double-blind multicenter phase IIb/III trial with 63 case registries, which did not make a significant difference in OS (study group 25 months, placebo group 31 months), the total removal group showed excellent clinical results (3-year survival rate; 65%, median survival; not reached). Since the study was designed to go to Phase III if the test group was not inferior to the placebo group, so it went on to go to Phase III.METHODSTarget patients will be 80 patients with newly diagnosed glioblastoma undergoing pathologic diagnosis, who have undergone total removal of contrast-enhanced lesions and receive standard chemoradiation therapy.STUDY DESIGNDouble-blind, 3-year enrollment period, 18-month observation period. Stratification factor: Photodynamic therapy (PDT), facility, age, KPS. Administration method: After standard chemoradiotherapy, in parallel with maintenance chemotherapy, a total of 9 times intradermal administration of vaccine. Primary endpoint: PFS of FAS patients, Secondary endpoints: 18 months PFS of the FAS patient, OS, PFS of the ITT analysis target case. Based on the results of the IIb trial, we limited the registered patients with total tumor removal, and in view of the fact that the prognosis of patients with combined PDT and AFTV were excellent, PDT was added to the stratification factor. We outline our efforts and problems aimed at clinical approval of AFTV for glioblastoma.

IM-01 PI3K GAMMA INHIBITOR FOR OVERCOMING TREATMENT RESISTANCE IN COMBINATION THERAPY OF TEMOZOLOMIDE AND ANTI-PDL1 ANTIBODY FOR GLIOBLASTOMA PATIENTS

PURPOSEMultidisciplinary therapies including immunotherapy in glioblastoma (GBM) patients often cause long survivor, while early relapse of GBM still remains. We should find factors associated with the immunotherapy-resistance for overcoming it. We previously reported that the infiltration of PD-1 positive cells and M2 macrophages (M2M&phi) increased in recurrent specimens compared to the initial specimens of GBMs treated with chemo-radiotherapy and autologous formalin-fixed tumor vaccine. Here we evaluate whether combination of novel immunotherapies, anti-PD-L1 antibody and M2M&phi inhibitor (IPI-549) inhibits growth of temozolomide (TMZ)-treated glioma cells rather than monotherapy. METHODSUsing murine glioma initiating cells (TS) and TMZ-resistant TS (TMZRTS) cells, PD-L1 expression and cytokine production associated with M2M&phi were evaluated. TMZRTS cells were implanted in mice flank, followed by anti-PD-L1 antibody and / or IPI-549 administration.RESULTSRelative cell proliferation rate of TMZRTS cells was lower than TS cells, while PD-L1 mRNA expression was higher. Treatment with PD-L1 antibody caused marked infiltration of M2M&phi in glioma tissue. The combination therapy strongly inhibited tumor growth in TMZRTS murine model.CONCLUSIONThe anti-PD-L1 antibody treatment altered tissue microenvironment including marked infiltration of macrophages in glioma tissue, probably associated with clinical immunotherapy-resistance in GBM. Combination therapy with anti-PD-L1 antibody and M2M&phi inhibitor could overcame it.

Abstract 5634: Eradication of breast carcinoma with bone metastasis by autologous formalin-fixed tumor vaccine (AFTV) combined with radiation and chemotherapy

Abstract No standardized treatment has been established for skeletal metastasis of breast carcinoma which is refractory to intensive chemo-radiation therapy and therefore is assumed impossible to cure. Here we show, however, the 3rd successful case concomitantly treated with the tumor vaccine, AFTV, and chemo-radiation therapy (the 1st and 2nd cases have been presented in AACR2013 and AACR2015, respectively). A 50-year old woman presented 2.5-cm mass of tubular carcinoma in her left breast in a MRI image. The tumor accompanied with no lymph node metastasis was resected in March 2009. We found the tumor was ER(+), PgR(-), and HER2 (-). Four months after the resection, she selected one course of AFTV as the first-line therapy. Response to delayed-type hypersensitivity (DTH) test became strongly positive. We then treated her with the aromatase inhibitor, anastrozole. Six years later, in March 2015, a PET image revealed bone-metastasis to sternum which was confirmed by needle-biopsy and ABC immunostaining as class V metastatic ductal carcinoma. We treated her again with second course of AFTV and palliative radiation therapy (36Gy/12fractions/19days) together with letrozole, bisphosphonate, additional 2 shots of nivolmab (40mg/48kg body) in October and November 2015. She was diagnosed to be complete response by PET imaging in February 2016, August 2016, and August 2017. Alteration of her blood CEA level suggests that the combined treatments eradicated the metastatic breast carcinoma. In conclusion, the present case suggests that AFTV in combination with palliative X-ray irradiation and adjuvant aromatase inhibitors eradicates skeletal metastasis of breast carcinoma with enhancement of a specific anti-tumor immune reactivity. Citation Format: Fumito Kuranishi, Yuki Imaoka, Hiroshi Iwako, Yoji Uemae, Takeshi Ishihara, Tsubasa Miyazaki, Tadao Ohno. Eradication of breast carcinoma with bone metastasis by autologous formalin-fixed tumor vaccine (AFTV) combined with radiation and chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5634.

Rate of Clinical Complete Response for 1 Year or More in Bone-Metastatic Breast Cancer after Comprehensive Treatments including Autologous Formalin-Fixed Tumor Vaccine.

Introduction No effective treatment has been developed for bone-metastatic breast cancer. We found 3 cases with clinical complete response (cCR) of the bone metastasis and longer overall survival of the retrospectively examined cohort treated comprehensively including autologous formalin-fixed tumor vaccine (AFTV). Patients and Methods AFTV was prepared individually for each patient from their own formalin-fixed and paraffin-embedded breast cancer tissues. Results Three patients maintained cCR status of the bone metastasis for 17 months or more. Rate of cCR for 1 year or more appeared to be 15% (3/20) after comprehensive treatments including AFTV. The median overall survival time (60.0 months) and the 3- to 8-year survival rates after diagnosis of bone metastasis were greater than those of historical control cohorts in Japan (1988–2002) and in the nationwide population-based cohort study of Denmark (1999–2007). Conclusion Bone-metastatic breast cancer may be curable after comprehensive treatments including AFTV, although larger scale clinical trial is required.

Vaccine Therapy of High-Grade Gliomas.

Multiple phase II clinical trials on the use of tumor vaccines in cases of high-grade gliomas (HGG), in particular autologous formalin-fixed tumor vaccine (AFTV), demonstrated the safety and potential efficacy of such therapy. There is evidence that maximal resection of neoplasm provides optimal conditions for enhancement of the tumor-specific immune reactions induced by vaccine administration, and thus aggressive surgery may be an important prerequisite for treatment success. Irradiation and chemotherapy may also enhance the effectiveness of vaccines, particularly through modulation of the tumor microenvironment. Nevertheless, the most effective combinations of vaccine therapies with surgery, irradiation, chemotherapy, antiangiogenic therapy, or other modes of immunotherapy in cases of HGG are still unclear and likely to be an active area of research in the future.

Long-lasting complete response status of advanced stage IV gall bladder cancer and colon cancer after combined treatment including autologous formalin-fixed tumor vaccine: two case reports

BackgroundThe prognosis of advanced (stage IV) cancer of the digestive organs is very poor. We have previously reported a case of advanced breast cancer with bone metastasis that was successfully treated with combined treatments including autologous formalin-fixed tumor vaccine (AFTV). Herein, we report the success of this approach in advanced stage IV (heavily metastasized) cases of gall bladder cancer and colon cancer.Case presentationCase 1: A 61-year-old woman with stage IV gall bladder cancer (liver metastasis and lymph node metastasis) underwent surgery in May 2011, including partial resection of the liver. She was treated with AFTV as the first-line adjuvant therapy, followed by conventional chemotherapy. This patient is still alive without any recurrence, as confirmed with computed tomography, for more than 5 years.Case 2: A 64-year-old man with stage IV colon cancer (multiple para-aortic lymph node metastases and direct abdominal wall invasion) underwent non-curative surgery in May 2006. Following conventional chemotherapy, two courses of AFTV and radiation therapy were administered sequentially. This patient has had no recurrence for more than 5 years.ConclusionWe report the success of combination therapy including AFTV in cases of liver-metastasized gall bladder cancer and abdominal wall-metastasized colon cancer. Both patients experienced long-lasting, complete remission. Therefore, combination therapies including AFTV should be considered in patients with advanced cancer of the digestive organs.

Abstract 1699: Impact of whole blood interferon gamma production for patient selection in vaccination with autologous formalin-fixed tumor vaccine

Abstract Introduction: Immune checkpoint blockade by anti-CTLA-4 antibody and anti-PD-1 antibody led to clinical breakthrough for the treatment of patients with solid tumors. Moreover, recent reports have shown that neoantigens are important functional targets mediating response to immune checkpoint inhibitors. Therefore, sequential combination of personalized cancer vaccines and immune checkpoint blockade has emerged as a potential therapeutic strategy. However, existing drawbacks is that it is difficult to identify robust biomarkers for patient selection in vaccination with cancer vaccine. In this study, we examined whether the development of delayed-type hypersensitivity (DTH) response, measured after vaccination with autologous formalin-fixed tumor vaccine (AFTV), correlates to parameters of immune function such as whole blood cytokine levels and peripheral regulatory T cells (Treg) in patients with solid tumors. Methods: Subjects comprised 52 patients with solid malignancy. AFTV treatment consisted of 3 courses of vaccination performed at intervals of 2 weeks. DTH test was performed before and after vaccination. A positive DTH response was defined as a ≥ 10mm diameter erythema/induration. We evaluated whole blood cytokine production after phytohemagglutinin (PHA) stimulation using the bioplex array system. We also assessed the number of peripheral Tregs as well as routine hematological and biochemical parameters. Results: DTH positive patients and DTH negative patients did not differ with respect to the number of peripheral Tregs, leukocytes, lymphocytes or granulocyte/lymphocyte ratio. Whole blood IFN-γ production levels after phytohemagglutinin (PHA) stimulation at baseline in DTH positive patients were significantly higher than those in DTH negative patients (p=0.0397). Conclusion: These data indicate that whole blood IFN-γ production at baseline is likely to be useful to assess immunologic competence in vaccinated patients with AFTV. Consequently, clinical utility of whole blood IFN-γ production, as immunomonitoring method for patient selection in vaccination with cancer vaccine, is required to investigate in larger clinical studies in the future. Citation Format: Naoyuki Sakamoto, Takeshi Ishikawa, Tetsuya Okayama, Tomoyo Yasuda, Toshifumi Doi, Mari Tanigawa, Yuji Naito, Yoshito Itoh, Toshikazu Yoshikawa. Impact of whole blood interferon gamma production for patient selection in vaccination with autologous formalin-fixed tumor vaccine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1699. doi:10.1158/1538-7445.AM2017-1699

Assessment of PD-1 positive cells on initial and secondary resected tumor specimens of newly diagnosed glioblastoma and its implications on patient outcome.

Glioblastoma (GBM) is the most common type of malignant brain tumor and has a very poor prognosis. Most patients relapse within 12 months despite aggressive treatment and patient outcome after recurrent is extremely worse. This study was designed to clarify the change of the molecular expression, including programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1), on the initial and secondary resected tumor specimens and to address the influence of these expressions for patient outcome after second surgery of glioblastoma. We investigated 16 patients, ranging in age from 14 to 65 years, with histologically verified WHO grade IV GBM, whose original tumor was resected between 2008 and 2014, and treated with fractionated radiotherapy and temozolomide. Four patients who were treated with immunotherapy using autologous formalin-fixed tumor vaccine were enrolled. All of the patients underwent secondary resection after tumor recurrence within 24 months. We carried out an immunohistochemical examination of the initial and secondary resected tumors from patients using a panel of immune system molecular markers, and assessed whether marker expression correlated with clinical outcomes. CD3, CD8 and PD-1 on tumor-infiltrating lymphocytes was significantly increased in secondary resected specimens compared with initially resected specimens (p ≤ 0.05). All patients expressed PD-L1 on tumor cells in initial and secondary resection specimens. Patients were divided into high or low expression group by median IHC score of PD-1 on initial or secondary resected specimens. No significant differences in patient outcomes were observed between high and low PD-1 or PD-L1 groups of initially resected specimens. In high expression group of secondary resected specimens, most patients score had increased which compared with initial resected tumor specimens. The PD-1 high expression score group of secondary resected specimens was associated with long progression-free survival and short survival after recurrence. PD-L1 expression was detected in almost all initial and secondary specimens. Patients with high PD-1 expression of secondary specimen had bad prognosis after secondary resection. PD-1/PD-L1 pathway may be associated with patient outcome after second surgery of glioblastoma.

OS09.8 Randomized placebo-controlled trial of autologous formalin-fixed tumor vaccine for newly diagnosed glioblastoma

Abstract Introduction: There is a growing interest in development of novel therapeutic modalities based on tumor-specific immune reactions for management of glioblastoma multiforme (GBM). Autologous formalin-fixed tumor vaccine (AFTV) was designed by our group for in vivo induction of killer lymphocytes and activation of T-lymphocyte (Nat Med 1995, 1996). In first trial for recurrent GBM, 3 responding patients survived more than 20 months after AFTV administration (Cancer Sci, 2007). Efficacy of AFTV concomitant with fractionated radiotherapy (FRT) without chemotherapy with temozolomide (TMZ) in patients with newly-diagnosed GBM was evaluated in prospective phase I/IIa trial (2), which showed median overall survival (OS) of 19.8 months (J Neurosurg, 2011). Another prospective multicenter phase I/IIa trial (UMIN01426) for evaluation of the combined use of AFTV and standard chemoradiotherapy with TMZ (AFTV+RT/TMZ: (Stupp regimen) for newly-diagnosed GBM, showing median progression-free survival (PFS) and OS of 8.2 and 22.2 months, respectively (J Neurosurg, 2013). Currently, prospective multicenter placebo-controlled double-blind phase IIb/III trial (UMIN10602) directing on evaluation of AFTV+RT/TMZ for newly-diagnosed GBM is ongoing and recruiting of patients for its phase IIb part has been finished in January 2016. We here report preliminary results before a key opening. METHODS: The phase IIb/III study investigated the AFTV plus chemoradiotherapy with temozolomide (AFTV + RT/TMZ; Stupp protocol) versus placebo plus chemoradio- therapy (Pla + RT/TMZ) for newly diagnosed glioblastoma. After resection surgery, patients with glioblastoma were randomly assigned 1:1 to receive AFTV (2 courses; 3 times, once a week) + RT/TMZ or Pla + RT/TMZ until disease progression. The primary end point was overall survival (OS), and secondary end points were progression-free survival (PFS), objective response rate, QOL, and safety. RESULTS: Adult 63 patients with supratentrial glioblastoma were enrolled, although 3 patients withdraw the consents. Among 60 patients for full analysis set, baseline characteristics were balanced. The median age was 61 years old, men vs. women were 33 vs. 27, and the median resection rate was 95%. Mean follow-up period was 15.8 months. The median PFS was 14.2 months and 6-month PFS was 75% both for AFTV+RT/TMZ and Pla+RT/TMZ. The median PFS was 21.4 months and 1-year survival was 86% both for AFTV+RT/TMZ and Pla+RT/TMZ. No severe adverse events caused by AFTV or placebo were observed. CONCLUSION: The phase IIb part of the trial has been done safely and trial would be promising because the median PFS for both groups was more than a year. If AFTV+RT/TMZ would show longer survival time compared to Pla+RT/TMZ by the key open, a phase III would be warranted.

Abstract 2236: Long lasting CR status of stage IV gall bladder cancer and colon cancer after combined treatment including autologous formalin-fixed tumor vaccine (AFTV)

Abstract (INTRODUCTION) The prognosis of advanced (stage IV) cancer is very poor. However, we have already reported two cases of eradication of advanced breast cancer with bone metastasis (AACR 2013 and AACR 2015) after combined treatments including AFTV. We here additionally report successful cases of gall bladder cancer (stage IV, liver metastasis) and colon cancer (stage IV, lung metastasis). (CASE 1) A 61-year-old female with stage IV gall bladder cancer (T3N1M1: liver metastasis) was operated in May 2011 including partial resection of liver. She was treated with, as the first-line adjuvant therapy, AFTV followed with conventional chemotherapy. This patient is still alive without any recurrence confirmed by CT etc. (CASE 2) A 60 year-old male with stage IV (N3, H0, P1, M1: lung, lt. adrenal gland, abdominal wall) was operated in August 2009. Then conventional chemotherapy, 2 courses of AFTV and radiation were applied sequentially. No recurrence was observed for more than 5 years. (DISCUSSION) We diagnosed both patients staying at long lasting complete remission. The prognoses of stage IV gall bladder cancer and abdominal wall-metastasized colon cancer are very poor despite of conventional treatments. Adverse effects of AFTV were less than grade 2, therefore combination therapies including AFTV are worth to consider, although larger scale clinical trial is essential. Citation Format: Fumito Kuranishi, Yusuke Sumi, yoij Uemae, Tadao Ohno. Long lasting CR status of stage IV gall bladder cancer and colon cancer after combined treatment including autologous formalin-fixed tumor vaccine (AFTV). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2236.

IMPS-23RETROSPECTIVE ANALYSIS CLINICAL RESULTS OF AUTOLOGOUS FORMALIN-FIXED TUMOR VACCINE FOR NEWLY DIAGNOSED GLIOBLASTOMA

There has been a growing interest in therapeutic modalities based on tumor-specific immune reactions for glioblastoma (GBM). Autologous formalin-fixed tumor vaccine (AFTV) for GBM is an emerging innovative treatment approach, which aims at stimulating patient's own immune system. We retrospectively analyzed clinical results of vaccine treatment patients. 63 cases of newly diagnosed GBM cases with concomitant AFTV treatment on the 1st line therapy were analyzed comparing with 100 cases of control group without AFTV during 2000 ∼ 2013. Newly diagnosed GBM with KPS > 60, 16-75yo, more than 80% removal were enrolled for the analysis. Three courses of AFTV was administered after initial treatment of chemo- and radiation. Overall survival (OS) and progression free survival (PFS) were analyzed. mOS of AFTV group and control group were 31.3 months and 20.6 months (p = 0.01). mPFS were 14.0 months and 9.8 moths (p = 0.037). OS of delayed-type hypersensitivity(DTH) positive group was 31.6 months comparing with 15.4 months in negative group(p = 0.063). multivariate analysis showed significant association in KPS (HR 1.84). The results of this study demonstrate the feasibility of AFTV as concomitant treatment of 1st line therapy. We are ongoing multicenter double-blind prospective randomized phase II/III trial.

Abstract 2492: Eradication of breast cancer with bone metastasis by autologous formalin- fixed tumor vaccine (AFTV) and radiation

Abstract INTRODUCTION) Bone-metastatic mammary carcinoma patients show the downhill course to a tragic ending despite of intensive chemo-radiation therapy, except an our case concomitantly treated with AFTV (AACR2013, World J Surg Oncol 2013; 11:127). We here report, as the second successful case, eradication of a large bone metastasis of advanced breast cancer after treatment with AFTV and radiation. (CASE) A 47-years old female with stage II breast cancer was operated in July, 2000. Left axillar recurrence was found 13 years later by ultrasonography and FNBC. PET scan revealed a huge bone metastasis in sternum. She was treated with radiation and AFTV (J Neurosurgery 2014;4:1) in Oct. - Nov. 2013. Follow-up PET (Sep. 2014) showed no hot spot, and we diagnosed the patient, complete remission. (CONCLUSION) Complete remission of bone metastasis of mammary carcinoma is very rare. The initial successful case beared triple-negative breast cancer. Treatment with AFTV and radiation without intensive chemotherapy like the present case will be acceptable to any patient with bone-metastatic mammary carcinoma, though a large scale clinical trial should be required to confirm the therapeutic efficacy of AFTV. Citation Format: Fumito Kuranishi, Yoji Uemae, Tadao Ohno, Yusuke Sumi. Eradication of breast cancer with bone metastasis by autologous formalin- fixed tumor vaccine (AFTV) and radiation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2492. doi:10.1158/1538-7445.AM2015-2492

Phase I/IIa trial of chemoradiotherapy plus autologous formalin-fixed tumor vaccine for newly diagnosed glioblastoma: Association between complete resection and delayed-type hypersensitivity response.

e13029 Background: We report a prospective phase I/IIa clinical trial of fractionated radiotherapy (FRT) concomitant with Temozolomide (TMZ) , followed by autologous formalin-fixed tumor vaccine (A...

Eradication of breast cancer with bone metastasis by autologous formalin-fixed tumor vaccine (AFTV) combined with palliative radiation therapy and adjuvant chemotherapy: a case report

Skeletal metastasis of breast carcinoma is refractory to intensive chemo-radiation therapy and therefore is assumed impossible to cure. Here, we report an advanced case of breast cancer with vertebra-Th7 metastasis that showed complete response to combined treatments with formalin-fixed autologous tumor vaccine (AFTV), palliative radiation therapy with 36 Gy, and adjuvant chemotherapy with standardized CEF (cyclophosphamide, epirubicin, and 5FU), zoledronic acid, and aromatase inhibitors following mastectomy for the breast tumor. The patient has been disease-free for more than 4 years after the mammary surgery and remains well with no evidence of metastasis or local recurrence. Thus, a combination of AFTV, palliative radiation therapy, and adjuvant chemotherapy may be an effective treatment for this devastating disease.

Abstract 471: A case of bone-metastatic breast cancer resulted in complete remission 5 years after the comprehensive treatment including autologous formalin-fixed tumor vaccine.

Abstract Introduction: All cases, so far we have experienced,of bone-metastatic breast carcinoma patients show the downhill course to a tragic ending despite of intensive chemo-radiation therapy. We here report a case of advanced breast cancer that has been additively treated with autologous formalin-fixed tumorvaccine (AFTV) (Clin Cancer Res 10: 1574-9 2004). Case : A 53 years old female was diagnosed bearing a bone metastasis of breast cancer at vertebra Th7 by bone scintigraphy, MRI and SPECT. The breast was operated, irradiated according to palliative radiation therapy with 36 Gy, vaccinated with AFTV, and then chemotherapy (CEF) was done as the last step of adjuvant therapy. Afterwards aromatase inhibitor and zoledronic acid hydrate was used for maintenance therapy. Five years later, the bonemetastasis has disappeared and she was diagnosed complete remission. Tumor markers have been in normal level . QOL of this patient is good at present. Conclusion: Complete remission of bone metastasis of breast carcinoma is very rare. In this case, the preceded use of AFTV and radiation to the chemotherapy may have contributed to the cure. Additional use of AFTV should be considered in a larger scale clinicaltrial to improve therapeutic efficacy in bone-metastatic breast carcinoma. Citation Format: Fumito Kuranishi, Tadao Ohno. A case of bone-metastatic breast cancer resulted in complete remission 5 years after the comprehensive treatment including autologous formalin-fixed tumor vaccine. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 471. doi:10.1158/1538-7445.AM2013-471

Erratum: Phase I/IIa trial of autologous formalin-fixed tumor vaccine concomitant with fractionated radiotherapy for newly diagnosed glioblastoma

Erratum: Phase I/IIa trial of autologous formalin-fixed tumor vaccine concomitant with fractionated radiotherapy for newly diagnosed glioblastoma

Autologous formalin-fixed tumor vaccine suppressed re-recurrence of HCV-related hepatocellular carcinoma following 29 unsuccessful treatments with extensive conventional therapy: a case report

Treatment of hepatocellular carcinoma (HCC) with autologous formalin-fixed tumor vaccine after primary resection has been shown to suppress the recurrence of hepatitis B virus-associated HCC, but the effect of this treatment on hepatitis C virus (HCV)-related disease has not yet been clarified. Here, we report a case of a patient with repeat recurrent HCC that was associated with HCV who had endured 29 episodes of HCC recurrence despite a variety of therapy using conventional methods. Finally, treatment with a single course of autologous formalin-fixed tumor vaccine resulted in suppression of potential further re-recurrence of HCC for more than 43 months without any additional treatment.