Tisagenlecleucel in Acute Lymphoblastic Leukemia: A Review of the Literature and Practical Considerations

Halford, Zachery; Anderson, Mary Kate; Bennett, Lunawati L; Moody, Jonathan

doi:10.1177/1060028020948165

Cited by 7 publications

(7 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The first FDA approved CAR-T cell therapy, Kymriah (tisagenlecleucel, CTL019), has achieved 12-month relapse-free survival rates of 55-59% in the treatment of acute lymphoblastic leukemia (ALL). 9 Yescarta (KTE-C19 axicabtagene ciloleucel) was approved shortly after Kymriah to treat diffuse large B-cell lymphoma (DLBCL) (NCT02529813). It achieved overall response rate of 83% and complete response rate of 58% in clinical trial.…”

Section: Car-t Cell Therapiesmentioning

confidence: 99%

Fibroblast Activation Protein (FAP)-Targeted CAR-T Cells: Launching an Attack on Tumor Stroma

Bughda¹,

Dimou²,

D'Souza³

et al. 2021

ITT

View full text Add to dashboard Cite

Fibroblast activation protein (FAP) is a membrane protease that is highly expressed by cancer-associated fibroblasts (CAFs). FAP can modulate the tumor microenvironment (TME) by remodeling the extracellular matrix (ECM), and its overexpression on CAFs is associated with poor prognosis in various cancers. The TME is in part accountable for the limited efficacy of chimeric antigen receptor (CAR)-T cell therapy in treatment of solid tumors. Targeting FAP with CAR-T cells is one of the strategies being researched to overcome the challenges in the TME. This review describes the role of FAP in the TME and its potential as a target in CAR-T cell immunotherapy, summarizes the preclinical studies and clinical trials of anti-FAP-CAR-T cells to date, and reviews possible optimizations to augment their cytotoxic efficiency in solid tumors.

show abstract

Section: Car-t Cell Therapiesmentioning

confidence: 99%

Fibroblast Activation Protein (FAP)-Targeted CAR-T Cells: Launching an Attack on Tumor Stroma

Bughda¹,

Dimou²,

D'Souza³

et al. 2021

ITT

View full text Add to dashboard Cite

show abstract

“…CAR-T therapy is an innovative and effective therapeutic option for the treatment of hematological malignancies refractory to previous treatment lines or multiple relapses [1][2][3][4][5][6][7][8][9][10]12,[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]32,34,[37][38][39][40][41][42][43][44][45][46].…”

Section: Discussionmentioning

confidence: 99%

“…It has been approved and recognized in many countries for its ability to prolong survival and disease-free periods with an appropriate level of safety. However, some of the adverse effects manifesting after the expansion of CAR-T cells have been a challenge for scientists and health professionals dedicated to the management of patients undergoing therapy [ 1 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 17 , 18 , 23 , 26 , 27 , 29 , 30 , 31 , 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…After leukocytapheresis and before the infusion of the cells, patients who are candidates for therapy should undergo a lymphodeplector chemotherapy regimen based on fludarabine and cyclophosphamide in order to control the disease until infusion and to allow subsequent clonal expansion [ 5 ]. The process of CAR-T therapy is represented in Figure 1 [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Interleukin Inhibitors in Cytokine Release Syndrome and Neurotoxicity Secondary to CAR-T Therapy

Ferreros¹,

Trapero²

2022

Diseases

View full text Add to dashboard Cite

Introduction: Chimeric antigen receptor T-cell (CAR-T) therapy is an innovative therapeutic option for addressing certain recurrent or refractory hematological malignancies. However, CAR-T cells also cause the release of pro-inflammatory cytokines that lead to life-threatening cytokine release syndrome and neurotoxicity. Objective: To study the efficacy of interleukin inhibitors in addressing cytokine release syndrome (CRS) and neurotoxicity secondary to CAR-T therapy. Methodology: The authors conducted a bibliographic review in which 10 articles were analyzed. These included cut-off studies, case reports, and clinical trials involving 11 cancer centers and up to 475 patients over 18 years of age. Results: Tocilizumab is the only interleukin inhibitor approved to address CRS secondary to CAR-T therapy due to its efficacy and safety. Other inhibitors, such as siltuximab and anakinra, could be useful in combination with tocilizumab for preventing severe cytokine release and neurotoxicity. In addition, the new specific inhibitors could be effective in mitigating CRS without affecting the cytotoxic efficacy of CAR-T therapy. Conclusion: More lines of research should be opened to elucidate the true implications of these drugs in treating the side effects of CAR-T therapy.

show abstract

“…This leads to their reduced recognition by cytotoxic T cells, and upregulation of inhibitory signals such as programmed cell death ligand PD‐L1, which reduces T cell activation and proliferation 16 . By genetically programming T cells with CAR targeting a tumour‐associated antigen irrespective of MHC expression (first‐generation CAR) and incorporating enhanced costimulatory domains to induce lymphocyte expansion (second‐generation CAR), 17 these diversionary tactics can be overcome in some cancers. The CAR T cells, once expanded ex vivo , can then be reintroduced into the patient where they target and kill cancer cells.…”

Section: Ex Vivo Cellular Gene Therapiesmentioning

confidence: 99%

Approved gene therapies in Australia: coming to a store near you

Mallik

Bailey

Rasko

2022

Internal Medicine Journal

View full text Add to dashboard Cite

Gene therapy has been promising paradigm-shifting advances in medical science for over two decades. Broadly, it is defined as a human therapy in which an existing defective gene function is added to, replaced, edited or disrupted to achieve a clinical benefit, up to and including a potential lifelong cure. Although originally set out to treat monogenic disorders, gene therapy has since been utilised to treat neoplasia, cardiovascular and neurodegenerative diseases, as well as infections. The realisation of this therapy has been dependent on the achievement of fundamental milestones in medicine, from determining the human genome sequence to identifying effective vehicles for the gene of interest, ultimately facilitating gene delivery in humans. In this review, six approved gene and cell therapies available in Australia are described. Their efficacy, adverse effects, limitations and eligibility are discussed, as well as an overview of cost and future directions.

show abstract

Tisagenlecleucel in Acute Lymphoblastic Leukemia: A Review of the Literature and Practical Considerations

Cited by 7 publications

References 66 publications

Fibroblast Activation Protein (FAP)-Targeted CAR-T Cells: Launching an Attack on Tumor Stroma

Fibroblast Activation Protein (FAP)-Targeted CAR-T Cells: Launching an Attack on Tumor Stroma

Interleukin Inhibitors in Cytokine Release Syndrome and Neurotoxicity Secondary to CAR-T Therapy

Approved gene therapies in Australia: coming to a store near you

Contact Info

Product

Resources

About