Targeting CNS Lymphoma with Intravenous Axicabtagene Ciloleucel: Evidence for Transcriptional Evolution Towards a Prominent Interferon Signature in CAR-T Cells Trafficking to the Tumor Site

Gerdemann, Ulrike; Kaminski, James J.; Albanese, Alexandre; Keskula, Paula; Cagnin, Lorenzo; Betz, Kayla; Zavistaski, Jillian; Fleming, Ryan A; Falvey, Caroline; Bouvier, Riemke; Jones, Julia; Poddar, Soumya; Mattie, Mike; Chukwueke, Ugonma; Torres, Alexandra; Jacobson, Caron A.; Nayak, Lakshmi; Kean, Leslie S.

doi:10.1182/blood-2022-166645

Cited by 2 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent evidence from anti-CD19 CAR T-cells have reassuringly shown that edited cells can be observed in the CSF of patients with acute lymphocytic leukemia [59], primary CNS lymphoma [60], and secondary CNS localizations in non-Hodgkin lymphoma [61], and that their presence is associated with high rates of response [62,63]. It is not clear though whether these findings also apply to anti-HIV CAR T-cells, and preclinical studies in animal models yielded discordant findings.…”

Section: Strategies Based On the Use Of Cellular Immunity Against Hiv...mentioning

confidence: 99%

Strategies to target the central nervous system HIV reservoir

Mastrangelo,

Gama,

Cinque

2024

Current Opinion in HIV and AIDS

View full text Add to dashboard Cite

Purpose of the review The central nervous system (CNS) is an hotspot for HIV persistence and may be a major obstacle to overcome for curative strategies. The peculiar anatomical, tissular and cellular characteristics of the HIV reservoir in the CNS may need to be specifically addressed to achieve a long-term HIV control without ART. In this review, we will discuss the critical challenges that currently explored curative strategies may face in crossing the blood–brain barrier (BBB), targeting latent HIV in brain-resident myeloid reservoirs, and eliminating the virus without eliciting dangerous neurological adverse events. Recent findings Latency reversing agents (LRA), broadly neutralizing monoclonal antibodies (bNabs), chimeric antigen receptor (CAR) T-cells, and adeno-associated virus 9-vectored gene-therapies cross the BBB with varying efficiency. Although brain penetration is poor for bNAbs, viral vectors for in vivo gene-editing, certain LRAs, and CAR T-cells may reach the cerebral compartment more efficiently. All these approaches, however, may encounter difficulties in eliminating HIV-infected perivascular macrophages and microglia. Safety, including local neurological adverse effects, may also be a concern, especially if high doses are required to achieve optimal brain penetration and efficient brain cell targeting. Summary Targeting the CNS remains a potential problem for the currently investigated HIV curing strategies. In vivo evidence on CNS effectiveness is limited for most of the investigated strategies, and additional studies should be focused on evaluating the interplay between the cerebral HIV reservoir and treatment aiming to achieve an ART-free cure.

show abstract

Section: Strategies Based On the Use Of Cellular Immunity Against Hiv...mentioning

confidence: 99%

Strategies to target the central nervous system HIV reservoir

Mastrangelo,

Gama,

Cinque

2024

Current Opinion in HIV and AIDS

View full text Add to dashboard Cite

show abstract

“…Our and other studies showed that Intracranial injection with steroids can be effective for severe ICANS 14 , 15 . Recently Ommaya capsule implantation is considerable and investigated in our and other clinical trials for r/r B-ALL and T-ALL patients with CNS mass 16 .…”

Section: Safety Managementmentioning

confidence: 99%

Chimeric Antigen Receptor T Cell Therapy for Acute Leukemia

2023

BCT

View full text Add to dashboard Cite

The worldwide use of CD19 chimeric antigen receptor (CAR)-T cells has increased the response rate in patients with refractory or relapsed B-cell acute lymphoblastic leukemia. Clinical practice has become much safer with the help of immunotherapy-related toxicity management guidelines, such as the ASTCT consensus grading system. Tocilizumab and steroids are the major interventions for controlling cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). New drugs and interventions for uncontrolled CRS and ICANS, including JAK1/2 inhibitors, have also been investigated. The combination of ruxolitinib and steroids effectively controlled severe CRS without impeding CAR-T cell expansion. Patients with refractory CNS3 status and CNS masses were excluded from the clinical trials because of the high risk of severe ICANS. Intracranial injections of steroids and Ommaya capsule implantation were effective. For some heavily treated patients, the difficulties in CAR-T cell manufacturing and expansion may be resolved by combination with blinatumumab. Relapse is a major concern after CAR-T therapy, and combination interventions, such as allogeneic stem cell transplantation, dual-target CAR-T cell therapies, and sequential CD19/22 CAR-T infusion, have been investigated in many centers. For T-lineage-targeted CAR-T therapies, the CAR T-cell fratricide can be overcome using many techniques. The efficacy and safety of CD7+ CAR-T cell therapy have been widely reported in recent years. A high response rate can be achieved when the immune reconstitution is prolonged. Infections, particularly viral reactivations, should be carefully monitored, as relapses are another potential issue. Switching targets and eliminating residual CD7+ CAR-T cells in the blood are key points for patients who relapse after CD7+ CAR-T cell therapy. CAR-T cell therapies for AML have not been investigated in a large-scale cohort, except for CD19-positive AML with the AML1-ETO fusion gene.

show abstract

Targeting CNS Lymphoma with Intravenous Axicabtagene Ciloleucel: Evidence for Transcriptional Evolution Towards a Prominent Interferon Signature in CAR-T Cells Trafficking to the Tumor Site

Cited by 2 publications

References 0 publications

Strategies to target the central nervous system HIV reservoir

Strategies to target the central nervous system HIV reservoir

Chimeric Antigen Receptor T Cell Therapy for Acute Leukemia

Contact Info

Product

Resources

About