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Article source: Medical Rubik's Cube Pro
Author: Bai Lu
Most new-onset acute lymphoblastic leukemia (ALL) in children and young adults can be cured, but patients with relapsed and/or refractory (r/r) ALL have a poor prognosis
.
Some new immunotherapies, including monoclonal antibodies, bispecific T cell adaptors and CAR-T cells, have changed the therapeutic prospects of r/r B-ALL
Since T-ALL itself is a T cell lesion, once it recurs, it progresses rapidly.
High tumor burden can inhibit the proliferation of normal T cells, which leads to the inability to collect enough healthy T cells
.
When CAR-T cells treat B-ALL, they will look for B cells with specific targets such as CD19 and CD22 to kill.
The good news is that several methods have been developed to avoid these problems, and encouraging preclinical data targeting CD2, CD5, CD7, and CD38 have prompted the opening of multiple early trials
.
Recently, the team of Director Pan Jing from Beijing Boren Hospital published an article in the Journal of Clinical Oncology, introducing the data of the first single-center phase I trial of r/r T-ALL with anti-CD7 CAR-T cell therapy, proving allogeneic health Donor-derived anti-CD7 CAR-T cells are safe and have an impressive short-term efficacy
.
In view of the limited number and quality of patient T cells, Pan Jing's team gave up using patient T cells to prepare CAR-T cells and switched to donor-sourced CD7 CAR-T cells to treat T-ALL
.
The trial initially only recruited adults, but after the initial safety certification was revised to include children in the scope of recruitment
Specifically, the trial was divided into two cohorts
.
1) The initial donor-derived T cell (PDD) cohort: Patients who have previously received hematopoietic stem cell transplantation (HSCT) with continuous donor chimera receive products from their initial donor
The dose of CAR-T therapy is 1×106 (±30%) CAR-T cells per kilogram
.
If the target dose is not enough due to collection or manufacturing problems, a lower dose (5×105 CAR-T cells per kilogram) can be infused to the patient
Of the 27 patients screened, 20 received treatment (12 in the PDD cohort and 8 in the NDD cohort): 19 cases of relapsed T-ALL, and 1 case of primary refractory T-ALL
.
The test results showed that 90% (n=18) of the patients achieved complete remission, and 7 patients continued to undergo stem cell transplantation
.
At a median follow-up of 6.
Source: Journal of Clinical Oncology
Adverse events included cytokine release syndrome (CRS) grade 1–2 90% (n=18), grade 3–4 10% (n=2), cytopenias grade 3–4 100% (n=20), neurological Toxicity 1-2 grade 15% (n=3), graft versus host disease (GvHD) grade 1-2 60% (n=12), virus activation grade 1-2 20% (n=4)
.
All adverse events were reversible, and only one patient died of fungal pneumonia 5.
At present, the rescue rate of r/r T-ALL patients is very low.
This is the first report that has been published to prove that donor-derived anti-CD7 CAR-T cells have shown effective expansion in this patient population and achieved a high degree of completeness.
Remission rate and controllable safety
.
However, due to the need to collect T cells from well-matched healthy donors, the donor-derived method used in this experiment is challenging, and how to commercialize it on a large scale is a problem
.
Given that donors will be treated as research subjects, some countries also need to overcome other regulatory hurdles
Scientists look forward to the long-term follow-up monitoring data of these patients to determine whether the remissions observed in this study are durable, and whether patients who have not received HSCT before CAR-T cell infusion can rebuild a functional immune system
.
This single-institution study only treated 20 patients, and the scientists are also looking forward to the ongoing multi-center Phase II trial (NCT04689659) of the therapy to bring more reference data
.
According to the NextPharma database of Medicine Rubik's Cube, there are 9 anti-CD7 CAR-T therapies currently entering the clinical stage, including this treatment from Beijing Boren Hospital
.
The fastest-growing companies include Accor Biology, Shenzhen Institute of Immunogene Therapy, and Wugen abroad.
The relevant candidate products are all in the phase I/II clinical stage
.
Source: NextPharma Database
Among them, the American biotechnology company Wugen completed US$172 million in Series B financing in July this year to promote the clinical progress of the next-generation product line including the allogeneic CD7 targeted CAR-T therapy for the treatment of T-ALL
.
Reference materials:
1# Jing Pan et al.
Donor-Derived CD7 Chimeric Antigen Receptor T Cells for T-Cell Acute Lymphoblastic Leukemia: First-in-Human, PhaseI Trial.
(2021) Journal of Clinical Oncology.
2# David T.
Teachey and Stephen P.
Hunger.
Anti-CD7 CAR T cells for T-ALL: impressive early-stage efficacy.
(2021) HAEMATOLOGICAL CANCER.
