Improving the therapeutic index in adoptive cell therapy: key factors that impact efficacy.
J Immunother Cancer
; 8(2)2020 10.
Article
en En
| MEDLINE
| ID: mdl-33023983
The therapeutic index (TI) is a quantitative assessment of a drug safety proportional to its effectiveness. The estimation is intuitive when the engagement of the product with its target is dependent on stable chemistry and predictable pharmacokinetics as is the case for small molecules or antibodies. But for therapeutics with complex biodistribution and context-dependent potency such as adoptive cell therapy (ACT) products, TI estimations need to consider a broader array of factors. These include product-dependent variability such as functional fitness, unpredictable pharmacokinetics due to non-specific trapping, sequestration and extravasation into normal tissues and variable rates of in vivo expansion. In the case of solid malignancies, additional modifiers dependent on individual tumor immune biology may affect pharmacodynamics, including differential trafficking to benign compared with cancer tissue, hampered engagement with target cells, immune suppression and cellular dysfunction due to unfavorable metabolic conditions. Here, we propose a patient-specific assessment of factors affecting on-tumor from off-tumor activity in disparate immunologic environments that impact ACT's clinical efficacy and may favorably balance the TI. for ACT products.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Inmunoterapia Adoptiva
/
Tratamiento Basado en Trasplante de Células y Tejidos
/
Inmunoterapia
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Immunother Cancer
Año:
2020
Tipo del documento:
Article
Pais de publicación:
Reino Unido