787. Non-Transmissible SeV Encoding Murine GM-CSF, Another Potent Vector System To Produce Autologous Tumor Vaccines

5081 Background: GM-CSF is a recombinant human cytokine, which increases the proliferation of granulocytes and monocytes. Experience with this agent, including adjuvant studies in melanoma, vaccine-based studies using autologous tumor vaccines that secrete human GM-CSF, and studies in prostate cancer using GM-CSF have all suggested that GM-CSF might provide anti-tumor activity in a subset of cancer patients. Methods: Open label phase II study performed in asymptomatic patients with recurrent mullerian malignancy without an indication for immediate systemic chemotherapy. Patients could have measurable or evaluable disease (defined as CA-125 >35 U/ml or 2 successively rising values with the most recent 3x the nadir value.) GM-CSF 250 mcg/m2 was administered subcutaneously on days 1–14 of a 28-day cycle. Monthly follow-up included interim history, physical exam and CA-125, with radiologic evaluation q 3 months. Results: Enrollment to this cohort is complete. Thirty-five women with a median age of 60 were enrolled; data are available on 33:30 women with ovarian and 3 with primary peritoneal cancers. To date 31 women are evaluable for response. Best overall response of patients who have completed the study includes 6 patients with stable disease (18%). Median time to treatment termination (TTT) was 76 days. Four patients remain on study, 2 with SD >6 months. Toxicity was generally mild, including injection site reaction, fatigue, and bone pain, however 2 patients experienced excessive toxicity and withdrew consent. There were 3 bowel obstructions thought related to disease but contribution of drug could not be ruled out. After 14 days of GM-CSF, CA-125 dropped in 23 of 33 women (70%) from their baseline on study value (median change -23%, range −48 to +158%). The magnitude of CA-125 drop during the first two weeks of therapy was significantly and positively correlated with day 15 WBC (p = 0.04.) Conclusions: GM-CSF is well tolerated and frequently associated with a decline in CA-125 that is correlated with leukocytosis. Although median TTT for the entire group is modest, a subset of women have had prolonged stable disease. Strategies to maintain and titrate leukocytosis are now being explored in a separate cohort. No significant financial relationships to disclose.

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Therapeutic benefit of adjuvant active specific immunotherapy (A.S.I.) with autologous tumor-vaccines in patients with colon cancer. Results of a randomised fase III study

Immunology Letters ◽

10.1016/s0165-2478(97)87692-4 ◽

1997 ◽

Vol 56 (1-3) ◽

pp. 214

Author(s):

A Claessen

Keyword(s):

Colon Cancer ◽

Specific Immunotherapy ◽

Therapeutic Benefit ◽

Autologous Tumor ◽

Tumor Vaccines ◽

Active Specific Immunotherapy

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Autologous tumor antigens and boron nanosheet-based nanovaccines for enhanced photo-immunotherapy against immune desert tumors

Nanophotonics ◽

10.1515/nanoph-2021-0229 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Zhe Sun ◽

Taojian Fan ◽

Quan Liu ◽

Luodan Huang ◽

Weibin Hu ◽

...

Keyword(s):

Immune Cells ◽

Tumor Antigens ◽

Photoacoustic Imaging ◽

Metastatic Potential ◽

Photothermal Effect ◽

Patient Specific ◽

Autologous Tumor ◽

Tumor Vaccines ◽

Therapeutic Vaccines ◽

Important Field

Abstract Personalized therapeutic vaccines against immune desert tumors are an increasingly important field in current cancer immunotherapy. However, limitations in neoantigen recognition, impotent immune cells, and a lack of intratumoral infiltrated lymphocytes pose challenges for the cancer vaccines. Resected tumors contain various of patient-specific tumor autoantigens (TA), and its derived photonanovaccines have unique competency to overcome abovementioned barriers. We constructed a novel personalized photonanovaccine (B@TA-R848) with surgically sourced TA modified on two-dimensional boron nanosheets (BNSs) via polydopamine coating and loaded with immune adjuvant R848. B@TA-R848 has good properties of drug delivery and release, photoacoustic imaging, photothermal effect, and biocompatibility. In a mouse triple-negative breast cancer model, B@TA-R848-based photonanovaccine induced effective systemic antitumor immune responses, altered the local tumor microenvironment, and increased the intratumoral infiltration of immune cells. The combined photo immunotherapy could significantly inhibit tumor growth, recurrence, and metastasis. This work develops a novel photonanovaccine for low immunogenicity and high metastatic potential tumors, which is of great significance for exploring the clinical development of personalized tumor vaccines against immune desert tumors.

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The Safety of an Adjuvanted Autologous Cancer Vaccine Platform in Canine Cancer Patients

Veterinary Sciences ◽

10.3390/vetsci5040087 ◽

2018 ◽

Vol 5 (4) ◽

pp. 87 ◽

Cited By ~ 1

Author(s):

Chris Weir ◽

Annika Oksa ◽

Jennifer Millar ◽

Miles Alexander ◽

Nicola Kynoch ◽

...

Keyword(s):

Adverse Reactions ◽

Tumor Antigens ◽

Autologous Tumor ◽

Tumor Vaccines ◽

Vaccine Platform ◽

Safety Study ◽

Diverse Range ◽

Canine Cancer ◽

Ongoing Development ◽

Vaccine Approach

Canine cancer rates are similar to humans, though the therapeutic options might be limited. Inducing a patient’s own immune system to have an anti-tumor response is an attractive approach to cancer therapy. In this safety study, autologous tumor vaccines produced specifically for each canine patient were combined with Advax™, a novel non-inflammatory immunomodulator and vaccine adjuvant and were tested for safety in a diverse range of patient presentations alone or in combination with other treatments. Canine patients had their tumor biopsied, debulked or resected and the tumor antigens were processed into an autologous vaccine formulated with Advax™ adjuvant with or without rhizavidin as an additional immune stimulant. Patients treated early in the trial received two intramuscular (IM) doses, 2 weeks apart. As the study progressed and no issues of safety were observed, the protocol was changed to weekly vaccinations for 4 weeks followed by monthly booster shots. Over the 150 I.M injections delivered to date, the vaccine was found to be very safe and no significant adverse reactions were observed. These results justify ongoing development and future controlled studies of this autologous vaccine approach.

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Novel Allogeneic Granulocyte-Macrophage Colony-Stimulating Factor–Secreting Tumor Vaccine for Pancreatic Cancer: A Phase I Trial of Safety and Immune Activation

Journal of Clinical Oncology ◽

10.1200/jco.2001.19.1.145 ◽

2001 ◽

Vol 19 (1) ◽

pp. 145-156 ◽

Cited By ~ 398

Author(s):

Elizabeth M. Jaffee ◽

Ralph H. Hruban ◽

Barbara Biedrzycki ◽

Daniel Laheru ◽

Karen Schepers ◽

...

Keyword(s):

Pancreatic Cancer ◽

Phase I Trial ◽

Tumor Vaccine ◽

Colony Stimulating Factor ◽

Tumor Vaccines ◽

Gm Csf ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor ◽

Disease Free

PURPOSE: Allogeneic granulocyte-macrophage colony-stimulating factor (GM-CSF)–secreting tumor vaccines can cure established tumors in the mouse, but their efficacy against human tumors is uncertain. We have developed a novel GM-CSF–secreting pancreatic tumor vaccine. To determine its safety and ability to induce antitumor immune responses, we conducted a phase I trial in patients with surgically resected adenocarcinoma of the pancreas. PATIENTS AND METHODS: Fourteen patients with stage 1, 2, or 3 pancreatic adenocarcinoma were enrolled. Eight weeks after pancreaticoduodenectomy, three patients received 1 × 107 vaccine cells, three patients received 5 × 107 vaccine cells, three patients received 10 × 107 vaccine cells, and five patients received 50 × 107 vaccine cells. Twelve of 14 patients then went on to receive a 6-month course of adjuvant radiation and chemotherapy. One month after completing adjuvant treatment, six patients still in remission received up to three additional monthly vaccinations with the same vaccine dose that they had received originally. RESULTS: No dose-limiting toxicities were encountered. Vaccination induced increased delayed-type hypersensitivity (DTH) responses to autologous tumor cells in three patients who had received ≥ 10 × 107 vaccine cells. These three patients also seemed to have had an increased disease-free survival time, remaining disease-free at least 25 months after diagnosis. CONCLUSION: Allogeneic GM-CSF–secreting tumor vaccines are safe in patients with pancreatic adenocarcinoma. This vaccine approach seems to induce dose-dependent systemic antitumor immunity as measured by increased postvaccination DTH responses against autologous tumors. Further clinical evaluation of this approach in patients with pancreatic cancer is warranted.

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