A Phase I, Open-label, Dose-escalation, and Cohort Expansion Study to Evaluate the Safety and Immune Response to Autologous Dendritic Cells Transduced With AdGMCA9 (DC-AdGMCAIX) in Patients With Metastatic Renal Cell Carcinoma

Expression of carbonic-anhydrase IX (CAIX) in clear cell renal cell carcinoma (RCC) makes it an attractive vaccine target. We developed a fusion-gene construct, granulocyte-macrophage (GM) colony-stimulating factor+CAIX, delivered by an adenoviral vector (Ad) into autologous dendritic cells (DCs) in this phase 1 study. The injected immature DCs were expected to stimulate an antigen-specific immune response against CAIX expressing RCC. Three dose-escalation cohorts (5, 15, and 50×106 cells/administration) were injected intradermally q2wk×3 doses based on a 3+3 design. The primary objective was the safety of the injections. Secondary objectives were immune responses using enzyme-linked immunosorbent spot, a serum biomarker panel, and clinical response. Fifteen patients with metastatic RCC were enrolled, and 9 patients received all 3 doses. No serious adverse events were seen. There were 3 (33%) patients with grade 1 fatigue, 1 of whom subsequently experienced grade 2 fatigue. One patient (11%) experienced grade 1–2 leukopenia. Only 1 patient (11%) experienced grade 2 flu-like symptoms. Of the 9 patients who received treatment, 1 expired of progressive disease, 2 patients were lost to follow-up and 6 patients are alive. Of the 6 patients, 5 have progressive disease, and 1 has completed treatment with stable disease at 27 months follow-up. Immune response measurements appeared more robust in higher dose cohorts, which appeared to be related to patients wi...
Source: Journal of Immunotherapy - Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

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hmidt-Wolf There is growing interest in cytokine-induced killer (CIK) cells on the integrated therapy of patients with RCC, especially those in the late stage or refractory to conventional chemotherapy and radiotherapy. In this review, a total of 15 clinical studies including 681 patients enrolled in CIK cell immunotherapy were outlined. Three-hundred-and-eighty-two patients with RCC were treated with CIK cells alone or in combination with DC vaccination, targeted agents sunitinib or sorafenib, and the PD-1 inhibitor pembrolizumab. Significantly improved 3-year overall survival rate was reported in four trials, whereas...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Cancer immunotherapy is a success story of translational medicine that has led to improved survival in patients with different difficult-to-treat types of cancer, such as metastasized melanoma, non-small cell lung cancer or renal cell carcinoma. These novel therapeutic agents exert their antitumor effects by activating the patients' immune system against cancer cells. Immunotherapy can be divided into active agents, such as anti-tumour vaccines or adoptive T-cell transfer, and passive immunotherapies like monoclonal antibodies, checkpoint inhibitors, cytokine therapy, bispecific T-cell engagers.
Source: International Journal of Cardiology - Category: Cardiology Authors: Source Type: research
Abstract Brain metastasis (BM) is associated with a poor prognosis, with the typical overall survival rate ranging from weeks to months in the absence of treatment. Although the concept of immune privilege in the central nervous system has eroded over time, the advent of immunotherapy has opened a new set of potential therapeutic options for patients with BM. Recently, immunotherapy has been demonstrated to confer survival advantages to patients with multiple malignancies commonly associated with BMs. Data from a number of clinical trials have demonstrated that immune checkpoint inhibitors are effective for patien...
Source: International Journal of Oncology - Category: Cancer & Oncology Authors: Tags: Int J Oncol Source Type: research
CONCLUSIONS: The experimental results of this study exhibited that the DNA vaccine based on heterogeneous chimeric antigen can produce efficient anti-tumor effect in vivo and they represent a promising strategy for tumor immunotherapy. PMID: 32706085 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research
aff Immunotherapy encompasses a wide range of therapies to engage the immune system to target malignancies. In recent years, immunotherapy has made a major impact on treatment of metastatic cancer and has altered standard of care for many tumor types. However, predicting and understanding responses across tumor types has been challenging. While some metastatic cancers have shown dramatic responses to immunotherapy, such as melanoma, lung cancer, and renal cell carcinoma, prostate cancer has generally failed to show a significant response. However, small series of prostate cancer patients have shown impressive responses...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Authors: Alhalabi O, Rafei H, Bilen MA, Shah AY Abstract The past decade has witnessed a revolution of immune checkpoint inhibitors in the treatment of multiple tumor types, including genitourinary cancers. Immune checkpoint inhibitors improved the treatment outcomes of patients with metastatic renal cell carcinoma and metastatic urothelial carcinoma. In prostate cancer, the role of immunotherapy with checkpoint inhibitors is not yet established, but clinical trials investigating their use are ongoing. Other immunotherapeutic approaches that have been explored in these malignancies include cytokines, vaccines, and ...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
ConclusionsCurrent clinical trials are exploring combination therapy and novel treatment strategies beyond immune checkpoint therapies and vaccine therapy such as CAR T cells. There is also an effort to establish synergy between immunotherapy and current standard of care. Furthermore, recent advances in personalized neoantigen vaccines suggest a shift towards personalized, patient-specific GBM treatment.
Source: Journal of Neuro-Oncology - Category: Cancer & Oncology Source Type: research
This study showed that carefully selected patients with locally advanced and metastatic forms of malignant melanoma and renal cell carcinoma could potentially have long-term disease control with a tag-7 gene-modified tumor cells-based vaccine. Randomized clinical trials in patients whose tumors produce low amounts of immunosuppressive factors are needed to confirm this hypothesis in both the adjuvant and metastatic settings. Graphic expression of the quantitative content of immunosuppressive factors in the supernatants of cultures of tumor cells of patients with sufficient and insufficient clinical effect. ABBREVIATIO...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
This study presents a case of prostate carcinoma and the tumour remission observed after administration of a personalised Dendritic cell vaccine (APCEDEN). Patient concerns: A 58 years old Caucasian male diagnosed with prostate carcinoma with GLEASON score 8. The patient had previously been diagnosed with Renal Cell Carcinoma (RCC) in 1996 and had undergone nephrectomy of the right kidney. PET CT scan revealed multiple intensely PSMA avid lesions noted in both lobes of the prostate gland with SUVmax −28.3 and the prostate gland measuring 3.2 × 3.2 cm displaying maximum dimensions. Diagnosis: FNAC fo...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
ConclusionIn conclusion, riavex as an anti-cancer vaccine is relatively safe in heavily pre-treated solid cancer patients and is assessed to improve quality of life, although the treatment response is not promising.Legal entity responsible for the studyThe author.FundingHas not received any funding.DisclosureThe author has declared no conflicts of interest.
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
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