Abstract CT032: A first-in-human phase I/II clinical trial assessing novel mRNA-lipoplex nanoparticles for potent cancer immunotherapy in patients with malignant melanoma

Podoplanin (PDPN), a small transmembrane mucin-like glycoprotein, is ectopically expressed on tumor cells. PDPN is known to be linked with several aspects of tumor malignancies in certain types of human and canine tumors. Therefore, it is considered to be a novel therapeutic target. Monoclonal antibodies targeting PDPN expressed in human tumor cells showed obvious anti-tumor effects in preclinical studies using mouse models. Previously, we generated a cancer-specific mouse–dog chimeric anti-PDPN antibody, P38Bf, which specifically recognizes PDPN expressed in canine tumor cells. In this study, we investigated the safety and anti-tumor effects of P38Bf in preclinical and clinical trials. P38Bf showed dose-dependent antibody-dependent cellular cytotoxicity against canine malignant melanoma cells. In a preclinical trial with one healthy dog, P38Bf administration did not induce adverse effects over approximately 2 months. In phase I/II clinical trials of three dogs with malignant melanoma, one dog vomited, and all dogs had increased serum levels of C-reactive protein, although all adverse effects were grade 1 or 2. Severe adverse effects leading to withdrawal of the clinical trial were not observed. Furthermore, one dog had stable disease with P38Bf injections. This is the first reported clinical trial of anti-PDPN antibody therapy using spontaneously occurring canine tumor models.

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Abstract CT156: A first-in-human phase I/II clinical trial assessing novel mRNA-lipoplex nanoparticles encoding shared tumor antigens for immunotherapy of malignant melanoma

10.1158/1538-7445.am2018-ct156 ◽

2018 ◽

Author(s):

Robert A. Jabulowsky ◽

Carmen Loquai ◽

Heidrun Mitzel-Rink ◽

Jochen Utikal ◽

Christoffer Gebhardt ◽

...

Keyword(s):

Clinical Trial ◽

Malignant Melanoma ◽

Phase I ◽

Tumor Antigens

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Phase I/II clinical trials of dendritic cell-based immunotherapy in patients with the biochemical relapse of the prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e16002 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e16002-e16002 ◽

Cited By ~ 1

Author(s):

Radek Spisek ◽

Michal Podrazil ◽

Marek Babjuk ◽

Ladislav Jarolim ◽

Jitka Fucikova ◽

...

Keyword(s):

Prostate Cancer ◽

Clinical Trial ◽

Dendritic Cells ◽

Dendritic Cell ◽

Phase I ◽

Cancer Immunotherapy ◽

Cell Line ◽

Peripheral Blood ◽

Disease Stage ◽

Biochemical Relapse

e16002 Background: In order to have the highest impact on the control of tumor growth, cancer immunotherapy should be initiated as early in the disease course as possible. In prostate cancer, the effect of cancer immunotherapy at the minimal residual disease stage can be evaluated in patients with the biochemical relapse detected by ultrasensitive PSA measurements. We performed a Phase I/II clinical trial of dendritic cell based immunotherapy in patients with the biochemical relaps of the prostate cancer. Methods: Patients with the prostate cancer in the biochemical failure after radical prostatectomy or primary radiotherapy were enrolled in the study. Study medication consisted of 12 doses of 1x107 dendritic cells pulsed with killed prostate cancer cell line LNCap (DCVAC/PCa), injected s.c. in 4 weeks intervals. Primary goal of the study was to assess the safety. Secondary goals were PSA kinetics and presence of tumor antigen specific immune response in the peripheral blood. Study is registered as EudraCT 2009-017259-91. Results: Twenty patients were enrolled in the study and evaluated after receiving complete treatment cycle of DCVAC/PCa. Administration of DCVAC/PCa did not lead to any significant side effects. Continuous cancer immunotherapy by DCVAC/PCa significantly prolonged the PSA doubling time (PSA-DT) in all treated patients, on average there was a 3,43-fold increase of PSA-DT after the completion of the treatment. Seven of 20 patients had stable PSA levels during the treatment duration. Mean PSA-DT increased from 8,15 months before the initiation of cancer immunotherapy to 52,64 months at the completion of 12 doses, p<0.0015. Sustained T cells responses against PSA, NY-ESO1, MAGE A1 and MAGE A3 were detected in the peripheral blood of enrolled patients. Conclusions: This study indicates that the continuous cancer immunotherapy with dendritic cells loaded with killed LNCAP cell line represents efficient treatment modality for prostate cancer patients with biochemical relapse. This study supports the use of immunotherapy early in the course of the disease, provided that relevant surrogate endpoints predictive of improved prognosis of early stage patients will be identified. Clinical trial information: 2009-017259-91.

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