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Published on: November 12, 2019
Anti-ROR1 CAR-T cells: Architecture and performance
Daniel Andrés Osorio-Rodríguez1, Bernardo Armando Camacho2, César Ramírez-Segura1,2
1Laboratorio de Investigación en Ingeniería Celular y Molecular, Instituto Distrital de Ciencia, Biotecnología e Innovación en Salud (IDCBIS), Bogotá, Colombia.
Abstract:
The receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a membrane receptor that plays a key role in development. It is highly expressed during the embryonic stage and relatively low in some normal adult tissues. Malignancies such as leukemia, lymphoma, and some solid tumors overexpress ROR1, making it a promising target for cancer treatment. Moreover, immunotherapy with autologous T-cells engineered to express a ROR1-specific chimeric antigen receptor (ROR1 CAR-T cells) has emerged as a personalized therapeutic option for patients with tumor recurrence after conventional treatments. However, tumor cell heterogeneity and tumor microenvironment (TME) hinder successful clinical outcomes. This review briefly describes the biological functions of ROR1 and its relevance as a tumor therapeutic target, as well as the architecture, activity, evaluation, and safety of some ROR1 CAR-T cells used in basic research and clinical trials. Finally, the feasibility of applying the ROR1 CAR-T cell strategy in combination with therapies targeting other tumor antigens or with inhibitors that prevent tumor antigenic escape is also discussed.
Clinical Trial Registration:
https://clinicaltrials.gov/, identifier NCT02706392.
Insights
Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a cancer target. ROR1 CAR-T cell therapy shows promise for treating recurrent cancers, but challenges like tumor heterogeneity require further research.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Biology
Background:
- Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is crucial in development and overexpressed in various malignancies.
- ROR1 presents a promising therapeutic target for cancer treatment due to its differential expression.
- Chimeric antigen receptor (CAR)-T cell therapy, specifically ROR1 CAR-T cells, offers a personalized approach for recurrent cancers.
Purpose of the Study:
- To review the biological functions and therapeutic relevance of ROR1.
- To discuss the development, evaluation, and safety of ROR1 CAR-T cells in research and clinical trials.
- To explore combination strategies to overcome challenges in ROR1 CAR-T cell therapy.
Main Methods:
- Review of existing literature on ROR1 biology and function.
- Analysis of ROR1 CAR-T cell designs, preclinical data, and clinical trial outcomes (e.g., NCT02706392).
- Discussion of ROR1's role in tumor microenvironment and heterogeneity.
Main Results:
- ROR1's significant role in embryonic development and aberrant expression in cancers like leukemia, lymphoma, and solid tumors.
- ROR1 CAR-T cells demonstrate potential as a personalized therapy for refractory malignancies.
- Tumor cell heterogeneity and the tumor microenvironment pose significant challenges to CAR-T cell efficacy.
Conclusions:
- ROR1 is a validated and attractive target for cancer immunotherapy.
- ROR1 CAR-T cell therapy is a viable strategy, but requires optimization to overcome resistance mechanisms.
- Combination therapies targeting ROR1 alongside other antigens or resistance pathways may enhance clinical outcomes.
