Successful monotherapy with autologous formalin-fixed tumor vaccine for a Stage IV uterine cancer patient who rejected rational chemotherapy and immune checkpoint inhibitor treatment.

Key Clinical Message: To overcome patient-initiated treatment refusal because of fear of experiencing severe negative adverse events, mild immunotherapy using a cancer vaccine such as the autologous formalin-fixed tumor vaccine should be considered.

Abstract: A patient who refused chemotherapy and immune checkpoint inhibitor treatment for Stage IV uterine cancer after displaying circulating tumor cells and high microsatellite instability received monotherapy with autologous formalin-fixed tumor vaccine (AFTV). Following treatment, we observed regression of multiple lung metastases, suggesting that AFTV is an attractive treatment option.

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

Objective: 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.

Methods: 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.

Synergistic anti-tumor efficacy of a hollow mesoporous silica-based cancer vaccine and an immune checkpoint inhibitor at the local site.

Immune checkpoint inhibitors elicit durable tumor regression in multiple types of tumor, but may induce potential side effects with low response rates in many tumors. Herein, to increase the therapeutic efficacy of immune checkpoint inhibitors, a hollow mesoporous silica (HMS) nanosphere-based cancer vaccine was combined with an immune checkpoint inhibitor, anti-programmed death-ligand 1 (anti-PD-L1) antibody. The HMS nanospheres function as adjuvants that promote dendritic cell activation and antigen cross-presentation.

Rod-Scale Design Strategies for Immune-Targeted Delivery System toward Cancer Immunotherapy.

Strengthening the antitumor immune response to surpass the activation energy barrier associated with the immunosuppressive tumor microenvironment is an active area of cancer immunotherapy. Emerging evidence suggests that delivery of immunostimulatory molecules with the aid of a carrier system is essential for cancer immunotherapy. However, the size-dependent effect of the delivery system on immune-targeted sites and anticancer immune responses is yet to be comprehensively understood.

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.

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.

Synergistic effects of stellated fibrous mesoporous silica and synthetic dsRNA analogues for cancer immunotherapy.

Stellated fibrous mesoporous silica nanospheres significantly improve the cellular uptake of cancer antigen and the maturation of bone marrow derived dendritic cells in vitro. Moreover, the combination of poly(I:C) with stellated fibrous MS nanospheres markedly decreases the necessary dose of poly(I:C) for anti-tumor immunity, and thus opens new opportunities for the future clinical application of poly(I:C) in cancer immunotherapy.

Complete remission of chemo-refractory multiple-metastatic upper tract urothelial carcinoma by autologous formalin-fixed tumor vaccine.

A patient with chemo-refractory multiple-metastatic upper tract urothelial carcinoma (UTUC) treated by monotherapy with autologous formalin-fixed tumor vaccine (AFTV) resulted in complete remission of the lung and para-aortic lymph node metastases (ongoing >3 years after AFTV). The tumor was immunohistologically negative for PD-L1. AFTV will be an attractive treatment option.

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.

Background: The 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.

A transient increase and subsequent sharp decrease of chemo-refractory liver-metastasized uterine cervical small cell carcinoma to autologous formalin-fixed tumor vaccine plus anti-PD-1 antibody.

Uterine cervical small cell carcinoma is rare and aggressive with no standardized therapy. A patient bearing the advanced chemo-refractory carcinoma, treated with a tumor vaccine combined with 1 mg/kg of pembrolizumab, showed a transient increase and subsequent sharp decrease of the liver-metastasized lesion to less than half its maximum diameter.

Cancer Immunotherapy: Comprehensive Mechanism Analysis of Mesoporous-Silica-Nanoparticle-Induced Cancer Immunotherapy (Adv. Healthcare Mater. 10/2016).

A plain mesoporous silica (MS) nanoparticle without any immunomodulatory molecules enhances anti-cancer immunity in vivo. On page 1169, X.P.

Hollow Structure Improved Anti-Cancer Immunity of Mesoporous Silica Nanospheres In Vivo.

Hollow and non-hollow mesoporous silica nanospheres are synthesized and used for cancer vaccine adjuvants. The hollow structure of mesoporous silica nanospheres significantly promote cellular uptake of a model cancer antigen by macrophage-like cells in vitro, improve anti-cancer immunity, CD4(+) and CD8(+) T cell populations in splenocytes of mice in vivo.

Comprehensive Mechanism Analysis of Mesoporous-Silica-Nanoparticle-Induced Cancer Immunotherapy.

A plain mesoporous silica nanoparticle without any immunomodulatory molecules significantly enhances anticancer immunity in vivo. Comprehensive mechanism of mesoporous-silica-nanoparticle-induced cancer immunotherapy is analyzed in this paper. The mesoporous silica nanoparticle promotes both Th1 and Th2 immune responses, as it accelerates lymphocytes proliferation, stimulates IFN-γ, IL-2, IL-4, and IL-10 cytokine secretion by lymphocytes ex vivo, and increases IgG, IgG1, IgG2a, IgM, and IgA antibody titers in mice serum compared with those of alum and adjuvant-free groups.

Rod-shaped and substituted hydroxyapatite nanoparticles stimulating type 1 and 2 cytokine secretion.

A Th1 immune response is required for modern vaccines as the most commonly used alum adjuvant has weak capacity for inducing Th1 immune response. Herein, rod-shaped hydroxyapatite (HA), magnesium-substituted HA (MgHA) and zinc-substituted HA (ZnHA) nanoparticles with irregular nanopores were synthesized and used as immunoadjuvants. Magnesium and zinc substitution in HA showed no influence on morphology, particle size, zeta potential and surface area of the nanoparticles.

Recurrent peritoneal serous carcinoma that was unmanageable with paclitaxel-carboplatin therapy responded to autologous formalin-fixed tumor vaccine.

Paclitaxel-carboplatin therapy (TC) usually controls primary peritoneal serous carcinoma (PPSC) but not recurrent disease. In this case, PPSC recurred after three courses of TC, responded dramatically to additional autologous formalin-fixed tumor vaccine (AFTV), and resulted in prolonged, progression-free survival without visible lesions detected by positron emission tomography-computed tomography.

Stimulation of In Vivo Antitumor Immunity with Hollow Mesoporous Silica Nanospheres.

The use of appropriate adjuvants that support the generation of robust and long-lasting antitumor immune responses is crucial for tumor immunotherapy owing to the immunosuppressive environment of the growing tumor. However, the most commonly used adjuvant, aluminum hydroxide, is ineffective for generating such immune responses and therefore not suitable for cancer immunotherapy. It is now shown that plain hollow mesoporous silica nanospheres markedly improve the antitumor immunity, the Th1 and Th2 immunity, and the CD4(+) and CD8(+) effector memory T cell population in bone marrow in vivo and may thus be used as immunoadjuvants to treat cancer in humans.

Suppression of postsurgical recurrence of hepatocellular carcinoma treated with autologous formalin-fixed tumor vaccine, with special reference to glypican-3.

Autologous formalin-fixed tumor vaccine (AFTV) suppressed re-recurrence for more than 32 months of multiple-recurrent hepatocellular carcinoma based on hepatitis C virus-induced liver cirrhosis in a case with previous recurrence interval, 51-, 28-, 12-, and 4-months. We detected glypican-3-specific cytotoxic T lymphocytes in the peripheral blood at 12 months after AFTV.

Phase I/IIa trial of fractionated radiotherapy, temozolomide, and autologous formalin-fixed tumor vaccine for newly diagnosed glioblastoma.

Object: Temozolomide (TMZ) may enhance antitumor immunity in patients with glioblastoma multiforme (GBM). In this paper the authors report on a prospective Phase I/IIa clinical trial of fractionated radiotherapy (FRT) concomitant with TMZ therapy, followed by treatment with autologous formalin-fixed tumor vaccine (AFTV) and TMZ maintenance in patients with newly diagnosed GBM.

Methods: Twenty-four patients (age 16-75 years, Karnofsky Performance Scale score ≥ 60% before initiation of FRT) with newly diagnosed GBM received a total dose of 60 Gy of FRT with daily concurrent TMZ.

A phase I study on combined therapy with proton-beam radiotherapy and in situ tumor vaccination for locally advanced recurrent hepatocellular carcinoma.

Background: Proton-beam radiotherapy (PBT) has been shown to be effective to hepatocellular carcinoma (HCC) as a nonsurgical local treatment option. However, HCC still remains as one of the most difficult cancers to be cured because of frequent recurrences. Thus, methods to inhibit the recurrence need to be explored.

Zn- and Mg- containing tricalcium phosphates-based adjuvants for cancer immunotherapy.

Zn-, and Mg-containing tricalcium phosphates (TCPs) loaded with a hydrothermal extract of a human tubercle bacillus (HTB) were prepared by immersing Zn-TCP and Mg-TCP in HTB-containing supersaturated calcium phosphate solutions. The in vitro and in vivo immunogenic activities of the HTB-loaded Zn-, and Mg-TCPs (Zn-Ap-HTB and Mg-Ap-HTB, respectively) were evaluated as potential immunopotentiating adjuvants for cancer immunotherapy. The Zn-Ap-HTB and Mg-Ap-HTB adjuvants showed no obvious cytotoxicity and more effectively stimulated granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion by macrophage-like cells than unprocessed HTB or HTB-loaded TCP (T-Ap-HTB) in vitro.

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.

Pore size-dependent immunogenic activity of mesoporous silica-based adjuvants in cancer immunotherapy.

Commonly used aluminum hydroxide (Alum) adjuvant provokes a strong type 2 helper T cell (Th2) response for mediating antibody production but is rather ineffective for disease prevention that requires type 1 helper T cell (Th1) response for mediating cellular immunity in human vaccination. Here, for the purpose of inducing Th1 antitumor immunity, a mesoporous silica (MS)-based adjuvant is prepared. Three kinds of MS particles with nearly identical particle size and surface area but different pore sizes of 4, 7 and 10 nm were prepared.