Leading Edge: Intratumor Delivery of Monoclonal Antibodies for the Treatment of Solid Tumors

Int J Mol Sci. 2023 Jan 31;24(3):2676. doi: 10.3390/ijms24032676.

Abstract

Immunotherapies based on immune checkpoint blockade have shown remarkable clinical outcomes and durable responses in patients with many tumor types. Nevertheless, these therapies lack efficacy in most cancer patients, even causing severe adverse events in a small subset of patients, such as inflammatory disorders and hyper-progressive disease. To diminish the risk of developing serious toxicities, intratumor delivery of monoclonal antibodies could be a solution. Encouraging results have been shown in both preclinical and clinical studies. Thus, intratumor immunotherapy as a new strategy may retain efficacy while increasing safety. This approach is still an exploratory frontier in cancer research and opens up new possibilities for next-generation personalized medicine. Local intratumor delivery can be achieved through many means, but an attractive approach is the use of gene therapy vectors expressing mAbs inside the tumor mass. Here, we summarize basic, translational, and clinical results of intratumor mAb delivery, together with descriptions of non-viral and viral strategies for mAb delivery in preclinical and clinical development. Currently, this is an expanding research subject that will surely play a key role in the future of oncology.

Keywords: intratumoral therapy; monoclonal antibodies (mAbs); non-viral therapy; viral therapy.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal* / therapeutic use
  • Humans
  • Immunotherapy / methods
  • Neoplasms* / drug therapy
  • Precision Medicine

Substances

  • Antibodies, Monoclonal

Grants and funding

The OncoImmunology group is funded by the Spanish Association against Cancer (AECC) (grant number PROYE16001ESCO); Instituto de Salud Carlos III (ISCIII)-FEDER project grants (grant numbers FIS PI17/02119, FIS PI20/00010, COV20/00000, TRANSPOCART ICI19/00069); a Biomedicine Project grant from the Department of Health of the Government of Navarre (grant number BMED 050-2019); strategic projects from the Department of Industry, Government of Navarre (AGATA, Ref. 0011-1411-2020-000013; LINTERNA, Ref. 0011-1411-2020-000033; DESCARTHES, 0011-1411-2019-000058); European Project Horizon 2020 Improved Vaccination for Older Adults (ISOLDA; ID: 848166). Crescendo Biologics Ltd. supported the OncoImmunology group for the development and testing of PD-1 and LAG-3 bispecific antibodies.