Skip to main content

GLP toxicology study of a fully-human T cell redirecting CD3:EGFRvIII binding immunotherapeutic bispecific antibody.

Publication ,  Journal Article
Gedeon, PC; Streicker, MA; Schaller, TH; Archer, GE; Jokinen, MP; Sampson, JH
Published in: PLoS One
2020

We recently reported the development of a fully-human, CD3-binding bispecific antibody for immunotherapy of malignant glioma. To translate this therapeutic (hEGFRvIII-CD3- bi-scFv) to clinical trials and to help further the translation of other similar CD3-binding therapeutics, some of which are associated with neurologic toxicities, we performed a good laboratory practice (GLP) toxicity study to assess for potential behavioral, chemical, hematologic, and pathologic toxicities including evaluation for experimental autoimmune encephalomyelitis (EAE). To perform this study, male and female C57/BL6 mice heterozygous for the human CD3 transgene (20/sex) were allocated to one of four designated groups. All animals were administered one dose level of hEGFRvIII-CD3 bi-scFv or vehicle control. Test groups were monitored for feed consumption, changes in body weight, and behavioral disturbances including signs of EAE. Urinalysis, hematologic, and clinical chemistry analysis were also performed. Vehicle and test chemical-treated groups were humanely euthanized 48 hours or 14 days following dose administration. Complete gross necropsy of all tissues was performed, and selected tissues plus all observed gross lesions were collected and evaluated for microscopic changes. This included hematoxylin-eosin histopathological evaluation and Fe-ECR staining for myelin sheath enumeration. There were no abnormal clinical observations or signs of EAE noted during the study. There were no statistical changes in food consumption, body weight gain, or final body weight among groups exposed to hEGFRvIII-CD3 bi-scFv compared to the control groups for the 2- and 14-day timepoints. There were statistical differences in some clinical chemistry, hematologic and urinalysis endpoints, primarily in the females at the 14-day timepoint (hematocrit, calcium, phosphorous, and total protein). No pathological findings related to hEGFRvIII-CD3 bi-scFv administration were observed. A number of gross and microscopic observations were noted but all were considered to be incidental background findings. The results of this study allow for further translation of this and other important CD3 modulating bispecific antibodies.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2020

Volume

15

Issue

7

Start / End Page

e0236374

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Single-Chain Antibodies
  • Mice
  • Male
  • Immunotherapy
  • Humans
  • Glioma
  • General Science & Technology
  • Female
  • ErbB Receptors
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Gedeon, P. C., Streicker, M. A., Schaller, T. H., Archer, G. E., Jokinen, M. P., & Sampson, J. H. (2020). GLP toxicology study of a fully-human T cell redirecting CD3:EGFRvIII binding immunotherapeutic bispecific antibody. PLoS One, 15(7), e0236374. https://doi.org/10.1371/journal.pone.0236374
Gedeon, Patrick C., Michael A. Streicker, Teilo H. Schaller, Gary E. Archer, Micheal P. Jokinen, and John H. Sampson. “GLP toxicology study of a fully-human T cell redirecting CD3:EGFRvIII binding immunotherapeutic bispecific antibody.PLoS One 15, no. 7 (2020): e0236374. https://doi.org/10.1371/journal.pone.0236374.
Gedeon PC, Streicker MA, Schaller TH, Archer GE, Jokinen MP, Sampson JH. GLP toxicology study of a fully-human T cell redirecting CD3:EGFRvIII binding immunotherapeutic bispecific antibody. PLoS One. 2020;15(7):e0236374.
Gedeon, Patrick C., et al. “GLP toxicology study of a fully-human T cell redirecting CD3:EGFRvIII binding immunotherapeutic bispecific antibody.PLoS One, vol. 15, no. 7, 2020, p. e0236374. Pubmed, doi:10.1371/journal.pone.0236374.
Gedeon PC, Streicker MA, Schaller TH, Archer GE, Jokinen MP, Sampson JH. GLP toxicology study of a fully-human T cell redirecting CD3:EGFRvIII binding immunotherapeutic bispecific antibody. PLoS One. 2020;15(7):e0236374.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2020

Volume

15

Issue

7

Start / End Page

e0236374

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Single-Chain Antibodies
  • Mice
  • Male
  • Immunotherapy
  • Humans
  • Glioma
  • General Science & Technology
  • Female
  • ErbB Receptors