Preclinical SC and IV repeat-dose toxicology of a cowpea mosaic virus – A cancer immunotherapy candidate

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Cancer immunotherapies focus on boosting the immune system to recognize and eliminate tumor cells. Amongst the various biologics under development for cancer immunotherapy, our team has focused on the study of plant viruses in this context. We have shown that intratumoral administration of cowpea mosaic virus (CPMV) relieves the immunosuppressive tumor microenvironment and elicits a potent, systemic and durable anti-tumor immune response. The potency of CPMV has been demonstrated in several tumor mouse models and in companion canine cancer patients. Toward clinical development, we here studied the pharmacology and safety of CPMV. The repeat-dose toxicity of CPMV was evaluated in female Sprague Dawley rats. Rats received three weekly treatments (subcutaneous or intravenous) of a fixed dose (∼20 mg/kg), and complete necropsy was performed either 24 hrs (acute toxicity group) or 14 day (recovery group) post-dose. All animals reached the scheduled euthanasia times, and no clinical abnormalities were noted during the study period. Important clinical chemistry, hematology and histopathology findings included decreased albumin/globulin ratio, leukocytosis, neutrophilia, monocytosis, and lymphoid hyperplasia (Dunnett’s test, p <0.05) – these changes support the immunostimulatory mode of action for CPMV. All other changes were considered mild, within historical range for the model, and/or not biologically significant. Neither a maximum tolerated dose (MTD) nor a no-observable adverse effect level (NOAEL) was established in this study. Overall, data indicate a good safety profile for the CPMV cancer immunotherapy candidate.

Graphical Abstract

Highlights

•

No deaths or abnormal clinical signs were observed during the study.
•

Immune activation markers support CPMV's immunostimulatory mechanism.
•

Other findings were mild, within historical range, or not biologically significant.
•

No MTD or NOAEL was established during the repeat-dose toxicity study.

Related collections

Most cited references 38

Record: found
Abstract: found
Article: not found

Delivery technologies for cancer immunotherapy

Rachel S Riley, Carl H. June, Robert C Langer … (2019)

Immunotherapy has become a powerful clinical strategy for treating cancer. The number of immunotherapy drug approvals has been increasing, with numerous treatments in clinical and preclinical development. However, a key challenge in the broad implementation of immunotherapies for cancer remains the controlled modulation of the immune system, as these therapeutics have serious adverse effects including autoimmunity and nonspecific inflammation. Understanding howto increase the response rates to various classes of immunotherapy is key to improving efficacy and controlling these adverse effects. Advanced biomaterials and drug delivery systems, such as nanoparticles and the use of T cells to deliver therapies, could effectively harness immunotherapies and improve their potency while reducing toxic side effects. Here, we discuss these research advances, as well as the opportunities and challenges for integrating delivery technologies into cancer immunotherapy, and we critically analyse the outlook for these emerging areas.

0 comments Cited 983 times – based on 0 reviews      Review now

Record: found
Abstract: found
Article: not found

Cancer immunotherapy comes of age.

George Coukos, Glenn Dranoff, Ira Mellman (2011)

Activating the immune system for therapeutic benefit in cancer has long been a goal in immunology and oncology. After decades of disappointment, the tide has finally changed due to the success of recent proof-of-concept clinical trials. Most notable has been the ability of the anti-CTLA4 antibody, ipilimumab, to achieve a significant increase in survival for patients with metastatic melanoma, for which conventional therapies have failed. In the context of advances in the understanding of how tolerance, immunity and immunosuppression regulate antitumour immune responses together with the advent of targeted therapies, these successes suggest that active immunotherapy represents a path to obtain a durable and long-lasting response in cancer patients.

0 comments Cited 832 times – based on 0 reviews      Review now

Record: found
Abstract: found
Article: not found

Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma.

Robert Andtbacka, Howard L. Kaufman, Frances A Collichio … (2015)

Talimogene laherparepvec (T-VEC) is a herpes simplex virus type 1-derived oncolytic immunotherapy designed to selectively replicate within tumors and produce granulocyte macrophage colony-stimulating factor (GM-CSF) to enhance systemic antitumor immune responses. T-VEC was compared with GM-CSF in patients with unresected stage IIIB to IV melanoma in a randomized open-label phase III trial.

0 comments Cited 645 times – based on 0 reviews      Review now

All references

Author and article information

Contributors

Nicole F. Steinmetz

Journal

Journal ID (nlm-ta): Toxicol Rep

Journal ID (iso-abbrev): Toxicol Rep

Title: Toxicology Reports

Publisher: Elsevier

ISSN (Electronic): 2214-7500

Publication date PMC-release: 07 April 2025

Publication date Collection: June 2025

Publication date (Electronic): 07 April 2025

Volume: 14

Electronic Location Identifier: 102022

Affiliations

[a ]Nanotechnology Characterization Lab, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD 21702, USA

[b ]Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, 9500 Gilman Dr., La Jolla, La Jolla, CA 92093, USA

[c ]Shu and K.C. Chien and Peter Farrell Collaboratory, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA

[d ]Center for Nano-ImmunoEngineering, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA

[e ]Department of Bioengineering, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA

[f ]Molecular Histopathology Laboratory, Laboratory of Animal Sciences Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, 8560 Progress Drive, Frederick, MD 21701, USA

[g ]Department of Radiology, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA

[h ]Institute for Materials Discovery and Design, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA

[i ]Moores Cancer Center, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA

[j ]Center for Engineering in Cancer, Institute of Engineering Medicine, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA

Author notes

[* ]Corresponding author at: Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, 9500 Gilman Dr., La Jolla, La Jolla, CA 92093, USA. nsteinmetz@ 123456ucsd.edu

Article

Publisher Item ID: S2214-7500(25)00140-4 Publisher ID: 102022

DOI: 10.1016/j.toxrep.2025.102022

PMC ID: 12019203

PubMed ID: 40276251

SO-VID: 255057d1-9e12-40c0-8fa4-af01984ce6f5

License:

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

History

Date received : 18 February 2025

Date revision received : 26 March 2025

Date accepted : 4 April 2025

Preclinical SC and IV repeat-dose toxicology of a cowpea mosaic virus – A cancer immunotherapy candidate

Read this article at