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Toxicity evaluation of ConvitVax breast cancer immunotherapy.

ABSTRACT: ConvitVax is a personalized vaccine for the treatment of breast cancer, composed of autologous tumor cells, bacillus Calmette-Guérin (BCG) and low concentrations of formalin. Previous pre-clinical studies show that this therapy induces a potent activation of the immune system and achieves an effective response against tumor cells, reducing the size of the tumor and decreasing the percentage of immunosuppressive cells. In the present study, we evaluate the toxicity of ConvitVax in healthy BALB/c mice to determine potential adverse effects related to the vaccine and each of its components. We used standard guidelines for pain, discomfort and distress recognition, continuously evaluated the site of the injection, and completed blood and urine clinical tests. Endpoint necropsy was performed, measuring the weight of organs and processing liver, kidney, thymus and lung for histological examination. Results show that the vaccine in its therapeutic dose, at 3 times its therapeutic concentration, and its individual components did not cause death or behavioral or biological changes, including any abnormalities in whole-body or organ weights, and tissue damage. These results support the safety of ConvitVax with minimal to no side-effects.

SUBMITTER: Duarte C MA

PROVIDER: S-EPMC8209199 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Toxicity evaluation of ConvitVax breast cancer immunotherapy.

Duarte C María A MA Carballo O Jeismar M JM De Gouveia Yetsenia M YM García Angie A Ruiz Diana D Gledhill Teresa T González-Marcano Eglys E Convit Ana F AF

Scientific reports 20210616 1

ConvitVax is a personalized vaccine for the treatment of breast cancer, composed of autologous tumor cells, bacillus Calmette-Guérin (BCG) and low concentrations of formalin. Previous pre-clinical studies show that this therapy induces a potent activation of the immune system and achieves an effective response against tumor cells, reducing the size of the tumor and decreasing the percentage of immunosuppressive cells. In the present study, we evaluate the toxicity of ConvitVax in healthy BALB/c ...[more]

PMID: 34135375

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Project description:Radiation-induced normal-tissue toxicities are common, complex, and distressing side effects that affect 90% of patients receiving breast-cancer radiotherapy and 40% of patients post radiotherapy. In this study, the authors investigated the use of spectrophotometry and ultrasound to quantitatively measure radiation-induced skin discoloration and subcutaneous-tissue fibrosis. The study's purpose is to determine whether skin discoloration correlates with the development of fibrosis in breast-cancer radiotherapy.Eighteen breast-cancer patients were enrolled in our initial study. All patients were previously treated with a standard course of radiation, and the median follow-up time was 22 months. The treated and untreated breasts were scanned with a spectrophotometer and an ultrasound. Two spectrophotometer parameters-melanin and erythema indices-were used to quantitatively assess skin discoloration. Two ultrasound parameters-skin thickness and Pearson coefficient of the hypodermis-were used to quantitatively assess severity of fibrosis. These measurements were correlated with clinical assessments (RTOG late morbidity scores).Significant measurement differences between the treated and contralateral breasts were observed among all patients: 27.3% mean increase in skin thickness (p < 0.001), 34.1% mean decrease in Pearson coefficient (p < 0.001), 27.3% mean increase in melanin (p < 0.001), and 22.6% mean increase in erythema (p < 0.001). All parameters except skin thickness correlated with RTOG scores. A moderate correlation exists between melanin and erythema; however, spectrophotometer parameters do not correlate with ultrasound parameters.Spectrophotometry and quantitative ultrasound are objective tools that assess radiation-induced tissue injury. Spectrophotometer parameters did not correlate with those of quantitative ultrasound suggesting that skin discoloration cannot be used as a marker for subcutaneous fibrosis. These tools may prove useful for the reduction of radiation morbidities and improvement of patient quality of life.

Project description:Immune checkpoints are small molecules expressed by immune cells that play critical roles in maintaining immune homeostasis. Targeting the immune checkpoints cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1) with inhibitory antibodies has demonstrated effective and durable antitumor activity in subgroups of patients with cancer. The US Food and Drug Administration has approved several immune checkpoint inhibitors (ICPis) for the treatment of a broad spectrum of malignancies. Endocrinopathies have emerged as one of the most common immune-related adverse events (irAEs) of ICPi therapy. Hypophysitis, thyroid dysfunction, insulin-deficient diabetes mellitus, and primary adrenal insufficiency have been reported as irAEs due to ICPi therapy. Hypophysitis is particularly associated with anti-CTLA-4 therapy, whereas thyroid dysfunction is particularly associated with anti-PD-1 therapy. Diabetes mellitus and primary adrenal insufficiency are rare endocrine toxicities associated with ICPi therapy but can be life-threatening if not promptly recognized and treated. Notably, combination anti-CTLA-4 and anti-PD-1 therapy is associated with the highest incidence of ICPi-related endocrinopathies. The precise mechanisms underlying these endocrine irAEs remain to be elucidated. Most ICPi-related endocrinopathies occur within 12 weeks after the initiation of ICPi therapy, but several have been reported to develop several months to years after ICPi initiation. Some ICPi-related endocrinopathies may resolve spontaneously, but others, such as central adrenal insufficiency and primary hypothyroidism, appear to be persistent in most cases. The mainstay of management of ICPi-related endocrinopathies is hormone replacement and symptom control. Further studies are needed to determine (i) whether high-dose corticosteroids in the treatment of ICPi-related endocrinopathies preserves endocrine function (especially in hypophysitis), and (ii) whether the development of ICPi-related endocrinopathies correlates with tumor response to ICPi therapy.

Dataset Information

Toxicity evaluation of ConvitVax breast cancer immunotherapy.

Publications

Toxicity evaluation of ConvitVax breast cancer immunotherapy.

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