Autologous CD7 CAR-T cells generated without T cell pre-selection in pediatric patients with relapsed/refractory T-ALL: A phase I trial.

Chimeric antigen receptor (CAR)-T cell therapy showed preliminary activity in patients with refractory or relapsed T cell acute lymphoblastic leukemia (r/r T-ALL). However, many obstacles remain, including manufacturing difficulties and risk of infections. This phase I study (NCT04840875) evaluated autologous CD7 CAR-T cells manufactured without pre-selection of healthy T cells in r/r T-ALL. Thirty patients (29 children and one adult) with a median of two lines of prior therapy but without detectable peripheral leukemia were enrolled. Excluding three cases of manufacturing failures, a total of 27 (90%) patients received infusions after products were confirmed free of leukemia contamination, including 16 (59%) meeting planned target doses. Common adverse events within 30 days included grade 3-4 cytopenias (100%), grade 1-2 (70%) and 3-4 (7%, including one dose-limiting toxicity) cytokine release syndrome, grade 1 neurotoxicity (7%), grade 2 infection (4%), and grade 2 graft-versus-host disease (4%). Two patients developed grade 2 infections after day 30. At day 30, 96% responded and 85% achieved complete remission (CR) or CR with incomplete hematologic recovery (CRi). Seventy-four percent underwent transplantation. Twelve-month progression-free survival with and without censoring transplantation was 22% (95% confidence interval 4%-100%) and 57% (41%-81%), respectively. These results support that autologous CD7 CAR-T therapy without T cell pre-selection is feasible in patients with r/r T-ALL.

InsT-ALLing CD7 chimeric antigen receptors before transplantation.

In their paper, the authors present their experience with the use of chimeric antigen receptor T cells targeting CD7 as a bridge to allogeneic haematopoietic cell transplantation in patients with relapsed/refractory T-cell acute lymphoblastic leukaemia/lymphoblastic lymphoma. Commentary on: Cao et al. A safety and efficacy study of allogeneic haematopoietic stem cell transplantation for refractory and relapsed T-cell acute lymphoblastic leukaemia/lymphoblastic lymphoma patients who achieved complete remission after autologous CD7 chimeric antigen receptor T-cell therapy. Br J Haematol 2024;204:2351-2364.

Characteristics and outcomes of acute myeloid leukaemia patients with baseline CD7 expression.

Targeted therapy development for acute myeloid leukaemia (AML) requires an understanding of specific expression profiles. We collected flow cytometry data on 901 AML patients and recorded aberrant CD7 expression on leukaemic blasts. 263 (29.2%) had blasts positive for CD7. CD7+ AML was more likely to be adverse risk (64.6% vs. 55.6%, p = 0.0074) and less likely to be favourable risk (15.2% vs. 24.1%, p = 0.0074) by European LeukemiaNet 2022 criteria. Overall survival was inferior (11.9 [95% CI, 9.7-15.9] vs. 19.0 months [95% CI, 16.1-23.0], p = 0.0174). At relapse, 30.4% lost and 19.0% gained CD7, suggesting moderate instability over time.

A safety and efficacy study of allogeneic haematopoietic stem cell transplantation for refractory and relapsed T-cell acute lymphoblastic leukaemia/lymphoblastic lymphoma patients who achieved complete remission after autologous CD7 chimeric antigen receptor T-cell therapy.

CD7-targeted chimeric antigen receptor T-cell (CAR-T) therapy has shown promising initial complete remission (CR) rates in patients with refractory or relapsed (r/r) T-cell acute lymphoblastic leukaemia and lymphoblastic lymphoma (T-ALL/LBL). To enhance the remission duration, consolidation with allogeneic haematopoietic stem cell transplantation (allo-HSCT) is considered. Our study delved into the outcomes of 34 patients with r/r T-ALL/LBL who underwent allo-HSCT after achieving CR with autologous CD7 CAR-T therapy. These were compared with 124 consecutive T-ALL/LBL patients who received allo-HSCT in CR following chemotherapy. The study revealed that both the CAR-T and chemotherapy cohorts exhibited comparable 2-year overall survival (OS) (61.9% [95% CI, 44.1-78.1] vs. 67.6% [95% CI, 57.5-76.9], p = 0.210), leukaemia-free survival (LFS) (62.3% [95% CI, 44.6-78.4] vs. 62.0% [95% CI, 51.8-71.7], p = 0.548), non-relapse mortality (NRM) rates (32.0% [95% CI, 19.0-54.0] vs. 25.3% [95% CI, 17.9-35.8], p = 0.288) and relapse incidence rates (8.8% [95% CI, 3.0-26.0] vs. 15.8% [95% CI, 9.8-25.2], p = 0.557). Patients aged ≤14 in the CD7 CAR-T group achieved high 2-year OS and LFS rates of 87.5%. Our study indicates that CD7 CAR-T therapy followed by allo-HSCT is not only effective and safe for r/r T-ALL/LBL patients but also on par with the outcomes of those achieving CR through chemotherapy, without increasing NRM.

Feasibility and preclinical efficacy of CD7-unedited CD7 CAR T cells for T cell malignancies.

Chimeric antigen receptor (CAR)-mediated targeting of T lineage antigens for the therapy of blood malignancies is frequently complicated by self-targeting of CAR T cells or their excessive differentiation driven by constant CAR signaling. Expression of CARs targeting CD7, a pan-T cell antigen highly expressed in T cell malignancies and some myeloid leukemias, produces robust fratricide and often requires additional mitigation strategies, such as CD7 gene editing. In this study, we show fratricide of CD7 CAR T cells can be fully prevented using ibrutinib and dasatinib, the pharmacologic inhibitors of key CAR/CD3ζ signaling kinases. Supplementation with ibrutinib and dasatinib rescued the ex vivo expansion of unedited CD7 CAR T cells and allowed regaining full CAR-mediated cytotoxicity in vitro and in vivo on withdrawal of the inhibitors. The unedited CD7 CAR T cells persisted long term and mediated sustained anti-leukemic activity in two mouse xenograft models of human T cell acute lymphoblastic leukemia (T-ALL) by self-selecting for CD7-, fratricide-resistant CD7 CAR T cells that were transcriptionally similar to control CD7-edited CD7 CAR T cells. Finally, we showed feasibility of cGMP manufacturing of unedited autologous CD7 CAR T cells for patients with CD7+ malignancies and initiated a phase I clinical trial (ClinicalTrials.gov: NCT03690011) using this approach. These results indicate pharmacologic inhibition of CAR signaling enables generating functional CD7 CAR T cells without additional engineering.

Decreased frequency of a novel T-lymphocyte subset, CD3+ CD4- CD7+ CD57- T cells, in hepatitis B virus-related end-stage liver disease might contribute to disease progression.

CD7 and CD57 are related to the differentiation and functional stages of CD8+ T cells. However, the role of their combined presence in CD8+ T cells in patients with chronic hepatitis B virus (HBV) infection, especially those with end-stage liver disease, remains unclear. Blood samples from healthy volunteers and patients with chronic hepatitis B were analyzed via Luminex assay and ELISA to measure plasma cytokine levels. Further, recombinant IL-22 was used to stimulate peripheral blood mononuclear cells from healthy volunteers, and the frequency of CD3+ CD4- CD7+ CD57- T cells and apoptosis rates were investigated via flow cytometry. Patients with end-stage liver disease, particularly those with acute to chronic liver failure, showed decreased CD3+ CD4- CD7+ CD57- T cell frequency. Furthermore, the prevalence of CD3+ CD4- CD7+ CD57- T cells was negatively correlated with disease severity, prognosis, and complications (ascites). We also observed that IL-22 promoted apoptosis and brought about a decrease in the number of CD3+ CD4- CD7+ CD57- T cells in a dose-dependent manner. CD3+ CD4- CD7+ CD57- T cells displayed a B and T lymphocyte attenuator (BTLA)high CD25high CD127high immunosuppressive phenotype and showed low interferon-γ, tumor necrosis factor-α, granzyme A, and perforin expression levels. The present findings will elucidate the pathogenesis of HBV-related end-stage liver disease and aid the identification of novel drug targets.

CD7 CAR T bridging to allo-HSCT in R/R T-ALL: A case report.

BACKGROUND: Refractory/relapsed T-cell acute lymphoblastic leukemia (R/R T-ALL) is a hematological malignancy with a poor prognosis. The current treatment strategy has not benefited most patients, and the treatment methods are still being explored. CASE PRESENTATION: An 8-year-old boy with R/R T-ALL achieved CR after multiple chemotherapies, followed by the first allo-HSCT. Unfortunately, 1 year and 3 months later, he relapsed. After recurrence, the patient underwent multiple chemotherapies, but the NOTCH1 gene and MRD were still positive. FCM and immunohistochemistry revealed abnormally high expression of CD7, so we considered bridging the second allo-HSCT after CD7 CAR T-cells treatment. The patient has low toxic and side effects and is still in CR, findings from this case report have more important therapeutic significance for R/R T-ALL. CONCLUSION: In conclusion, CD7 CAR T-cells bridging to allo-HSCT is a safe and effective approach for R/R T-ALL, resulting in durable CR and longer survival.

Blockade of costimulatory CD27/CD70 pathway promotes corneal allograft survival.

PURPOSE: To determine whether the CD27/CD70 pathway plays a significant role in corneal allograft rejection by investigating the effect of blocking the CD27/CD70 pathway by anti-CD70 antibody on corneal allograft survival. METHODS: Orthotopic penetrating keratoplasty was performed using C57BL/6 donor grafts and BALB/c recipients. Expression of CD27 and CD70 on rejected cornea was examined by immunohistochemistry. Corneal transplant recipients received intraperitoneal injection of anti-CD70 antibody (FR70) or control rat IgG. Alloreactivity was measured by mixed lymphoid reaction (MLR) in recipients administered control rat IgG and those administered anti-CD70 antibody. Corneal expression of IFN-γ and IL-12 was also examined in both groups. Graft opacity was assessed over an 8-week period and graft survival was evaluated using Kaplan-Meier survival curves. Proportion of CD4+CD44+ memory T cells in lymph nodes was measured by flow cytometry. RESULTS: CD4+CD27+ cells and CD11c+CD70+ cells were present in rejected cornea. Anti-CD70 antibody administration suppressed alloreactivity in corneal allograft recipients, and inhibited IFN-γ expression in recipient cornea (p < 0.05). Anti-CD70 antibody suppressed opacity score of recipient cornea and prolonged corneal allograft survival (p < 0.05). Proportion of CD4+CD44+ memory T cells in recipient lymph nodes was reduced by anti-CD70 antibody treatment. CONCLUSION: The CD27/CD70 pathway plays a significant role in corneal allograft rejection by initiating alloreactive Th1 cells and preserving memory T cells. Anti-CD70 antibody administration prolongs corneal allograft survival indicating the potential therapeutic effect of CD27/CD70 pathway blockade on corneal allograft rejection.

CD7 CAR T Cells for the Therapy of Acute Myeloid Leukemia.

Chimeric antigen receptor (CAR) T cell therapy for the treatment of acute myeloid leukemia (AML) has the risk of toxicity to normal myeloid cells. CD7 is expressed by the leukemic blasts and malignant progenitor cells of approximately 30% of AML patients but is absent on normal myeloid and erythroid cells. Since CD7 expression by malignant blasts is also linked with chemoresistance and poor outcomes, targeting this antigen may be beneficial for this subset of AML patients. Here, we show that expression of a CD7-directed CAR in CD7 gene-edited (CD7KO) T cells effectively eliminates CD7+ AML cell lines, primary CD7+ AML, and colony-forming cells but spares myeloid and erythroid progenitor cells and their progeny. In a xenograft model, CD7 CAR T cells protect mice against systemic leukemia, prolonging survival. Our results support the feasibility of using CD7KO CD7 CAR T cells for the non-myeloablative treatment of CD7+ AML.

Pediatric acute myeloid leukemia with t(7;21)(p22;q22).

The t(7;21)(p22;q22) resulting in RUNX1-USP42 fusion, is a rare but recurrent cytogenetic abnormality associated with acute myeloid leukemia (AML) and myelodysplastic syndromes. The prognostic significance of this translocation has not been well established due to the limited number of patients. Herein, we report three pediatric AML patients with t(7;21)(p22;q22). All three patients presented with pancytopenia or leukopenia at diagnosis, accompanied by abnormal immunophenotypic expression of CD7 and CD56 on leukemic blasts. One patient had t(7;21)(p22;q22) as the sole abnormality, whereas the other two patients had additional numerical and structural aberrations including loss of 5q material. Fluorescence in situ hybridization analysis on interphase cells or sequential examination of metaphases showed the RUNX1 rearrangement and confirmed translocation 7;21. Genomic SNP microarray analysis, performed on DNA extracted from the bone marrow from the patient with isolated t(7;21)(p22;q22), showed a 32.2 Mb copy neutral loss of heterozygosity (cnLOH) within the short arm of chromosome 11. After 2-4 cycles of chemotherapy, all three patients underwent allogeneic hematopoietic stem cell transplantation (HSCT). One patient died due to complications related to viral reactivation and graft-versus-host disease. The other two patients achieved complete remission after HSCT. Our data displayed the accompanying cytogenetic abnormalities including del(5q) and cnLOH of 11p, the frequent pathological features shared with other reported cases, and clinical outcome in pediatric AML patients with t(7;21)(p22;q22). The heterogeneity in AML harboring similar cytogenetic alterations may be attributed to additional uncovered genetic lesions.

The clinical importance of CD4+ CD7- in human diseases.

The CD7 antigen is a member of the immunoglobulin superfamily that expresses on the surface of all thymocytes, a majority of mature T cells, and also natural killer cells. Interestingly, under physiological and different pathological conditions, the loss of CD7 antigen occurred in the subset of CD4+ memory T cells. Various functions have been proposed for CD7, including its role in the activation and intercellular adhesiveness of T cells. Several studies indicate that the number of CD4+ CD7- T cells increases in diseases such as chronic inflammation and T-cell malignancies, these being skin inflammatory lesions. Therefore, this can be useful for the diagnosis of cancer cells, especially with reference to blood origin, treatment monitoring, and establishment of new therapies. Therefore, a comprehensive review could be useful to increase our knowledge about the clinical importance of these cells in human disease.

CD7 is expressed on a subset of normal CD34-positive myeloid precursors.

OBJECTIVE: To improve monitoring of myeloid neoplasms by flow cytometry-based minimal residual disease (MRD) analysis, we analyzed the significance of leukemia-associated immunophenotype (LAIP) markers in 44 patients. METHODS: In a pilot study cohort, peripheral blood or bone marrow samples from 13 patients with myeloid neoplasms and one case of B lymphoblastic leukemia in complete hematologic remission after allogeneic bone marrow or stem cell transplantation were subjected to selection for leukemia-specific phenotypes by fluorescence-activated cell sorting using individual marker combinations, followed by PCR-based chimerism analysis. RESULTS: The feasibility of this method could be demonstrated, with selection being successful in 12 cases, including two cases where mixed chimerism was found exclusively in sorted cells. Interestingly, four specimens displayed full donor chimerism in cells expressing the presumably aberrant combination CD34+ /CD7+ . Further analyses, including assessment of an independent cohort of 25 patients not affected by neoplastic bone marrow infiltration, revealed that normal myeloid precursors usually include a population coexpressing CD34, CD13, CD33, and CD7. CONCLUSION: We conclude that the combination CD34+ /CD7+ might not be suitable as an LAIP for MRD diagnostics and that a subset of normal myeloid precursors in the bone marrow expresses CD7.

Autocrine GM-CSF transcription in the leukemic progenitor cell line KG1a is mediated by the transcription factor ETS1 and is negatively regulated through SECTM1 mediated ligation of CD7.

BACKGROUND: CD7 expression is found on ~30% of acute myeloblastic leukemias (AML). The leukemic progenitor cell line KG1a (CD7+) constitutively expresses GM-CSF while the parental KG1 (CD7-) cell line does not. This study focuses on the molecular basis of CD7 mediated GM-CSF regulation. METHODS: KG1a cells were treated with recombinant SECTM1-Fc protein, the PI3K kinase inhibitors wortmannin, LY292004, or PI4K activator spermine. Stable KG1-CD7+, KG1a-shCD7, KG1a-shETS1 as well as KG1a-GFP, KG1a-PKCßII-GFP cell lines were generated and the levels of CD7, GM-CSF and ETS-1 mRNA and protein were compared by real-time-PCR, western blotting, flow cytometry and ELISA. RESULTS: SECTM1 is expressed in Human Bone Marrow Endothelial Cells (HBMEC) and its expression can be upregulated by both IFN-γ. KG1a cells demonstrated high expression levels of CD7 and ETS-1 allowing a constitutative signaling through the PI3K/Atk pathway to promote GM-CSF expression, while KG1 cells with low expression of CD7 and ETS-1 showed low GM-CSF expression. On KG1a cells GM-CSF expression could be negatively regulated by PI3K inhibitors or by recombinant SECTM1-Fc. Overexpression of CD7 in KG1 cells was insufficient to promote GM-CSF expression, while silencing of CD7 or ETS-1 resulted in reduced GM-CSF expression levels. Differentiation capable KG1a cells overexpressing PKCßII illustrated complete loss of CD7, but maintained normal levels of both ETS-1 and GM-CSF expression. CONCLUSION: These findings add an additional layer to the previously described autocrine/paracrine signaling between leukemic progenitor cells and the bone marrow microenvironment and highlight a role for SECTM1 in both normal and malignant hematopoiesis. GENERAL SIGNIFICANCE: This work shows that SECTM1 secreted from bone marrow stromal cells may interact with CD7 to influence GM-CSF expression in leukemic cells.

Advanced human T-cell leukemia virus type 1 carriers and early-stage indolent adult T-cell leukemia-lymphoma are indistinguishable based on CADM1 positivity in flow cytometry.

We previously reported that the cell adhesion molecule 1 (CADM1) versus CD7 plot in flow cytometry reflects disease progression in human T-cell leukemia virus type 1 (HTLV-1) infection. In CD4(+) cells from peripheral blood, CADM1(-) CD7(+) (P), CADM1(+) CD7(dim) (D) and CADM1(+) CD7(-) (N) subpopulations are observed. The D and N subpopulations increase as asymptomatic HTLV-1 carriers (AC) progress to indolent adult T-cell leukemia-lymphoma (ATL) and the N subpopulation then expands in aggressive ATL. In the present study we examined whether the analysis can estimate the risk of developing ATL in advanced AC. Peripheral blood samples from AC (N = 41) and indolent ATL patients (N = 19) were analyzed by flow cytometry using the CADM1 versus CD7 plot for CD4(+) cells and inverse long PCR (clonality analysis) of FACS-sorted subpopulations. Almost all AC with a high HTLV-1 proviral load (>4 copies/100 cells) had a CADM1(+) (D + N) frequency of >10%. AC with 25% < CADM1(+) ≤ 50% contained expanded clones similar to smoldering-type ATL. In many patients in the 25% < CADM1(+) ≤ 50% group, the proportion of abnormal lymphocytes was distributed around the 5% line, which divides AC and smoldering-type ATL in Shimoyama's classification. In conclusion, the CADM1 versus CD7 plot is useful for selection of putative high-risk AC. The characteristics of some AC and smoldering ATL are said to be similar; however, long-term follow up is required and the clinical outcome (e.g. rate of transformation) of these cases should be used to determine whether to include them in the same clinical category.

An Anti-CD7 Antibody-Drug Conjugate Target Showing Potent Antitumor Activity for T-Lymphoblastic Leukemia (T-ALL).

Acute T-lymphoblastic leukemia (T-ALL) is a type of leukemia that can occur in both pediatric and adult populations. Compared to acute B-cell lymphoblastic leukemia (B-ALL), patients with T-cell T-ALL have a poorer therapeutic efficacy. In this study, a novel anti-CD7 antibody-drug conjugate (ADC, J87-Dxd) was successfully generated and used for T-ALL treatment. Firstly, to obtain anti-CD7 mAbs, we expressed and purified the CD7 protein extracellular domain. Utilizing hybridoma technology, we obtained three anti-CD7 mAbs (J87, G73 and A15) with a high affinity for CD7. Both the results of immunofluorescence and Biacore assay indicated that J87 (KD = 1.54 × 10-10 M) had the highest affinity among the three anti-CD7 mAbs. In addition, an internalization assay showed the internalization level of J87 to be higher than that of the other two mAbs. Next, we successfully generated the anti-CD7 ADC (J87-Dxd) by conjugating DXd to J87 via a cleavable maleimide-GGFG peptide linker. J87-Dxd also possessed the ability to recognize and bind CD7. Using J87-Dxd to treat T-ALL cells (Jurkat and CCRF-CEM), we observed that J87-Dxd bound to CD7 was internalized into T-ALL cells. Moreover, J87-Dxd treatment significantly induced the apoptosis of Jurkat and CCRF-CEM cells. The IC50 (half-maximal inhibitory concentration) value of J87-Dxd against CCRF-CEM obtained by CCK-8 assay was 6.3 nM. Finally, to assess the antitumor efficacy of a J87-Dxd in vivo, we established T-ALL mouse models and treated mice with J87-Dxd or J87. The results showed that on day 24 after tumor inoculation, all mice treated with J87 or PBS died, whereas the survival rate of mice treated with J87-Dxd was 80%. H&E staining showed no significant organic changes in the heart, liver, spleen, lungs and kidneys of all mice. In summary, we demonstrated that the novel anti-CD7 ADC (J87-Dxd) had a potent and selective effect against CD7-expressing T-All cells both in vitro and in vivo, and could thus be expected to be further developed as a new drug for the treatment of T-ALL or other CD7-expression tumors.

CD7-positive leukemic blasts with DNMT3A mutations predict poor prognosis in patients with acute myeloid leukemia.

Background: DNMT3A mutations can be detected in premalignant hematopoietic stem cells and are primarily associated with clonal hematopoiesis of indeterminate potential; however, current evidence does not support assigning them to a distinct European Leukemia Net (ELN) prognostic risk stratification. CD7 is a lymphoid antigen expressed on blasts in approximately 30% of acute myeloid leukemia (AML), and its role in AML remains unclear and depends on subgroup evaluation. This study investigated the prognostic value of DNMT3A mutation combined with CD7 expression in AML. Methods: We retrospectively analyzed the clinical data of 297 newly diagnosed non-M3 AML patients. According to the DNMT3A mutation and CD7 expression in AML cells, patients were divided into the DNMT3A-mutated/CD7-positive (CD7+), DNMT3A-mutated/CD7-negative (CD7-), DNMT3A-wild-type/CD7+, and DNMT3A-wild-type/CD7- groups. Results: The DNMT3A-mutated/CD7+ group had lower complete remission rates and higher relapse rates. Importantly, these patients had significantly shorter overall survival (OS) and relapse-free survival (RFS). Furthermore, multivariate analysis showed that CD7+ with DNMT3A mutation was an independent risk factor for OS and RFS. Conclusion: CD7+ with DNMT3A mutation predicts a poor prognosis in AML patients, and the immunophenotype combined with molecular genetic markers can help to further refine the current risk stratification of AML.

Case report: Preventive infusion of donor-derived CD7 chimeric antigen receptor T cells after allogeneic hematopoietic stem cell transplantation.

Chimeric antigen receptor T cells (CAR T) targeting CD7 for T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) showed promising efficacy and safety in some clinical trials. However, most of them were bridged with allogeneic hematopoietic stem cell transplantation (allo-HSCT). We described successful treatment with preventive donor-derived anti-CD7 CAR-T therapy in a case of refractory T lymphoblastic lymphoma following allo-HSCT, who could not receive autologous anti-CD7 CAR-T products due to the low-quality of T lymphocytes. To date, the patient's complete remission has persisted for 20 months after HSCT.

Case report: Two pediatric cases of long-term leukemia-free survival with relapsed acute T-lymphoblastic leukemia treated with donor CD7 CAR-T cells bridging to haploidentical stem cell transplantation.

Introduction: Patients with relapsed/refractory (r/r) acute T-lymphoblastic leukemia (T-ALL) have a poor prognosis. We developed donor CD7 chimeric antigen receptor T (CAR-T) cells to salvage r/r T-ALL patients and obtained encouraging results. Patients who had not received allogeneic (allo-) hematopoietic stem cell transplantation (HSCT) before CAR-T therapy would develop pancytopenia and immunodeficiency for a long period after CD7 CAR-T therapy; therefore, allo-HSCT is needed in these patients. Here, we report two pediatric r/r T-ALL patients who received donor CD7 CAR-T bridging to allo-HSCT with leukemia-free survival (LFS) and sustained negative minimal residual disease for >2 years. Case presentation: Patient 1 was a 10-year-old boy who visited our hospital because of a T-ALL relapse with multiple lymphadenopathies without discomfort. The patient did not achieve remission after one course of induction chemotherapy. The patient then received donor (his father) CD7 CAR-T cells and achieved complete remission (CR). Thirty days after the first CAR-T cell infusion, he received allo-HSCT, and his father was also the donor. His LFS was >3 years. Patient 2 was an 8-year-old boy who was admitted to our hospital with relapsed T-ALL with fever, cough, and mild dyspnea. He did not achieve remission after one course of induction chemotherapy; therefore, he received donor (his father) CD7 CAR-T cells and achieved CR. Twenty-six days after CAR-T cell infusion, the patient received allo-HSCT, with his father as the donor. He has survived for >2 years free of leukemia. At the last follow up, both patients were alive and presented a good quality of life. Conclusion: The long-term survival of these two patients supports the use of CD7 CAR-T therapy bridging to allo-HSCT as an effective and safe treatment with the capacity to make r/r T-ALL a curable disease, similar to r/r acute B-lymphoblastic leukemia.

Stable engraftment, as well as graft versus host disease-free and relapse-free survival brought by the combination of CD7 targeted universal chimeric antigen receptor-T, and donor hemopoietic stem cells: Indication of a case report.

CD7 targeted CAR-T has demonstrated potential in the treatment of T cell malignancies but no study has been reported about its potential in the prophylaxis of GVHD in allo-HSCT. Here we reported a special case that a boy diagnosed with refractory acute T lymphoblastic leukemia (T-ALL) was treated with universal CD7 targeted CAR-T (CD7 UCAR-T) and parent-derived peripheral blood stem cells (PBSCs). Complete remission and full engraftment of donor was observed. In the later four months of follow-up, in the absence of any immunodepression treatment, no signs of GVHD were observed. This case initially demonstrates the potential of CD7 UCAR-T in the prophylaxis of GVHD.