Tecelra
afamitresgene autoleucel
Species
no relevantMouse
Longest study
none
Genotox
Not conducted Not conducted
Carcinogenicity
Not conducted Not conducted
Repro
Not conducted Not conducted
First dose
Not conducted Not stated publicly
Speciesopen answer page →
Species
No relevant species; in vitro cross-reactivity/alloreactivity and murine xenograft pharmacology only
“Standard in vivo single-dose or repeat-dose toxicity studies were not conducted with afamitresgene autoleucel due to the lack of appropriate animal models for testing of human TCR engineered T-cells.”
Why that species
HLA-restricted human TCR: MHC mismatch with animals; humanized mice develop lethal xeno-GvHD within 8 weeks
“Because afamitresgene autoleucel is an autologous engineered-TCR T-cell therapy, there is a mismatch of MHC antigens between animal and human TCRs, so specificity cannot be assessed.”
Surrogate molecule
No surrogate; engineering an animal TCR judged uninformative for human TCR specificity/safety
“Engineering an animal TCR for use in animal model testing would also not reflect the specificity/safety profile of the human TCR, and therefore would be uninformative.”
Study lengthopen answer page →
Longest pivotal study
0 (no in vivo tox study)
“Standard in vivo single-dose or repeat-dose toxicity studies were not conducted with afamitresgene autoleucel due to the lack of appropriate animal models for testing of human TCR engineered T-cells.”
Pivotal GLP studies
No in vivo tox; in vitro X-scan/MAGE-family peptide cross-reactivity, alloreactivity, normal/iPSC cell co-culture; murine xenograft efficacy
“A comprehensive analysis of cross-reactivity was performed using a peptide library screen with single amino-acid substitutions at each position of the antigenic peptide sequence (X-scan) and peptides from MAGE family member proteins.”
Route in tox
Not stated in public reviews
Skipped studiesopen answer page →
Genotoxicity
Not conducted (no test models or relevant species); integration site analysis showed polyclonal products, no selective insertion
“Conventional genotoxicity studies were not conducted with afamitresgene autoleucel, due to the lack of appropriate test models and pharmacologically relevant species.”
Carcinogenicity
Not conducted (no relevant animal models for human TCR-engineered T cells)
“Afamitresgene autoleucel is a human TCR engineered T-cell product, therefore conventional carcinogenicity studies were not performed due to the lack of relevant animal models.”
Reproductive & developmental
Not conducted; theoretical testis/placenta risk (MAGE-A4 expression) judged mitigated by immune privilege, labeling, pharmacovigilance
“MAGE-A4 is known to be expressed in testes and placenta, and so there is a theoretical risk of embryotoxicity or toxicity to the testes.”
Safety pharmacology
Not conducted; no relevant animal models
“No safety pharmacology studies were conducted, as there are no relevant animal models for the nonclinical safety assessment of afamitresgene autoleucel.”
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
NOAEL / key findings
No NOAEL; in vitro alloreactivity against HLA-A*02:05 (contraindication); cross-reactivity to MAGE-A8/MAGE-B2 (cancer/germline-restricted)
“An alloreactivity screen against a panel of cells expressing a range of HLA alleles indicated in vitro alloreactivity against HLA-A*02:05. Therefore, afamitresgene autoleucel is contraindicated for adults who are heterozygous or homozygous for HLA-A*02:05P.”
Risksopen answer page →
Immune & cytokine safety
In vitro cytokine-release assay for cytokine-storm risk, no concerns; no immunogenicity studies (wild-type human TCR)
“No immunogenicity studies have been performed on afamitresgene autoleucel, as there are no suitable animal models for assessment of the immunogenicity of human TCRs.”
Biodistribution & persistence
No PK/ADME studies; not considered relevant for autologous T-cell product
“Afamitresgene autoleucel, cell suspension for infusion is an autologous T-cell product. Therefore, traditional pharmacokinetic and ADME studies are not considered relevant to this product.”
Modality-specific risk
TCR off-target cross-reactivity and HLA alloreactivity; LV insertional oncogenesis (integration profile similar to other LV products)
“However, vector integration site analysis demonstrated that the insertion site profile for the product was similar to other lentiviral vector products and was not expected to represent a greater risk for the development of insertional oncogenesis.”