Which animal species did regulators accept for approved cell therapies?

“The PK and biodistribution of ide-cel were evaluated in NSG mice with and without BCMA+ xenografts.”

“Ide-cel comprises engineered human T cells, therefore there are no representative in vitro assays, ex vivo models, or in vivo models that can accurately address the toxicological characteristics of the human product.”

“The applicant has chosen immunocompromised athymic rats to perform the biodistribution, toxicology and tumourigenicity studies.”

“in order to minimize the immune recognition and potential rejection of human eASC in the experimental animal models and to extend Cx601 persistence”

“No nonclinical studies were conducted with AMTAGVI. Instead, the applicant cited published nonclinical data evaluating similar murine and human tumor-derived T lymphocytes to provide support for AMTAGVI.”

“No toxicology studies were conducted for AMTAGVI. Given the characteristics and biological activity of AMTAGVI, this omission is acceptable.”

“Per the applicant, conventional nonclinical toxicology studies were not conducted because they do not yield clinically relevant information for a CAR T cell product.”

“Aucatzyl, a patient-specific product, is not appropriate for administration to immunocompetent animals, as the T cells will not engraft.”

“In particular, suitable animal models are not available for accurately assessing the non-clinical characteristics of a human cell-based product such as JCAR017.”

“The results support that JCAR017 is specific for human CD-19 binding and lacks species cross-reactivity, in particular towards mouse and non-human primate.”

“Therefore, animal studies evaluating the safety profile of CARVYKTI™ were limited due to lack of a pharmacologically relevant animal species.”

“In vitro data indicate that does not significantly bind to recombinant mouse or NHP BCMA expressed on cells.”

“Non-clinical studies were performed as combined pharmacodynamic / pharmacokinetic (distribution) / toxicological studies in the ectopic mouse (nu/nu model) and in orthotopic models in sheep and goats.”

“orthotropic animal model showed that implantation of human or allogeneic chondrocytes causes an immune response to the CBMP, resulting in poor repair.”

“Safety pharmacology studies were not conducted due to the species-specific nature of tabelecleucel and the limited applicability of non-human toxicology models.”

“Because SCID mice are unable to generate functional lymphocytes, engraftment and growth of human lymphocytes and several human tumours are possible.”

“The effect of long-term ITV implantation of NT-501 was evaluated in a 3-part toxicology study in 4–8-month-old minipigs, 4–10-year-old pigs”

“Histopathologic studies in naturally occurring and genetically engineered animal models of photoreceptor dysfunction that phenotypically model retinitis pigmentosa support a role for rhCNTF”

“Species: Athymic mice, 6-8 weeks old; the number, strain and sex were not provided in the study report”

“The transplanted Apligraf® remained durable, as demonstrated by the persistence of human keratinocytes and fibroblasts, for at least one year in the nude mice.”

“Conventional non-clinical studies were generally not considered appropriate for Holoclar as a cell-based medicinal product (CBMP).”

“the lack of relevant animal models due to differences in the ocular structure of most other mammals.”

“The absence of GLP compliance is acceptable since standard single or repeat-dose toxicity studies could not be performed due to lack of a relevant animal model.”

“The lack of single-dose toxicity studies is acceptable, since tisagenlecleucel is a patient specific product, which is not appropriate to administer to immune competent animals.”

“No nonclinical studies were conducted with LANTIDRA.”

“The findings of these studies support inclusion of immunosuppression as a critical component for successful islet engraftment and survival following transplant in diabetic animals.”

“No preclinical studies were conducted with this product.”

“The BLA states that due to this previous commercial experience in humans, and due to the lack of a”

“Studies conducted in horses and rabbits compared ACI-Maix or empty defects to analogous products consisting of ACI-Maix seeded with rabbit or horse cells.”

“Implantation of MACI secured with a commercially available fibrin sealant resulted in improved repair of critical-sized defects in the knee/stifle”

“In vivo pharmacology, pharmacokinetic, and toxicology studies were conducted to evaluate the activity, distribution, and safety of the product in immunocompromised, irradiated mice.”

“Results showed that NOD/SCID mice were preferable over mice based on cell engraftment levels.”

“The immunogenicity and anti-tumour properties of these surrogate products were evaluated in rats and mice.”

“Animal models using species-specific variations of the human cell therapy product have been used.”

“Based on the acceptable clinical safety profile of RVT-802 and the lack of relevant animal species/models, no nonclinical toxicology studies with RVT-802 were performed.”

“Studies were conducted in nude rats to to identify potentially optimal culture conditions of allogeneic neonatal thymus that result in engraftment and development of an endogenous T cell population”

“The nonclinical program utilized multiple surrogate animal-derived ceMSC manufactured similarly to the clinical product.”

“This approach was taken to model administration of allogeneic ceMSCs in humans and evaluate the interactions between the cell product and recipient immune system.”

“Comparative analyses of chondrocytes from different species showed that only a limited number of animals including Göttinger mini-pig and Merino sheep were capable of producing stable spheroids.”

“These species were then selected for proof-of-concept studies.”

“The following toxicology study was conducted to evaluate the safety profile of STRATAGRAFT® following administration in an athymic (immunodeficient) murine wound model:”

“STRATAGRAFT® is composed of human cells, thus the potential for elicitation of a xenogeneic response following administration in immune competent animals exists.”

“Since the anti-CD19 scFv utilised for KTE-X19 does only recognise human CD19, a murine surrogate model was engineered for non-clinical proof-of-concept studies in immune competent mice.”

“Similar as the pharmacology evaluation, also the non-clinical safety evaluation of KTE-X19 has been severely limited due to the lack of a relevant animal model.”

“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.”

“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.”

“In the applicant’s POC studies using xenogeneic models, co-administration of human donor Tregs with Tcons demonstrated dose-dependent GVHD inhibition in sub-lethally irradiated immunodeficient mice.”

“evaluating the ability of human Tcons to induce xenogeneic GVHD”

“Single-dose toxicology studies in animals were not performed by the Applicant due to the lack of a relevant animal model.”

“Since the anti-CD19 scFv utilized for KTE-C19 does only recognize human CD19, a murine surrogate was engineered for non-clinical proof-of-concept studies in immune competent mice.”

“Two studies in two different GvHD animal models both based on the NOD/SCID system were performed to evaluate the PK and primary PD of MM-TK.”

“The MM-TK DP is a species specific product and therefore standard carcinogenicity studies using rodents or non-human primates as described in the ICH guidelines are not appropriate.”

“All in vivo studies have been conducted with female NSG mice.”

“because the applicant explained that UM171 had no activity on mouse HSCs (i.e. homologous murine product not possible).”