Evaluation of Patient Preference and Perception Regarding the Clinical Use of Autologous Versus Allogeneic Cell Therapy in Orthopedic Surgery

Background: Cell therapy has become a hot topic in orthopedics, with significant research dedicated to improving physicians’ understanding of its efficacy. However, little is known about patients’ cell therapy knowledge. Questions/Purposes: The aims of this study were to (1) evaluate patients’ perceptions of cell therapy in orthopedics, (2) determine whether patients have a preference for autologous or allogeneic cell therapy, and (3) assess patient concerns about cell therapy. Methods: Consecutive outpatients of an orthopedic clinic were surveyed from June 2019 to January 2020. All patients were 18 years old or older and being seen for an orthopedic intervention, including rotator cuff repair, anterior cruciate ligament (ACL) reconstruction, arthroscopic meniscectomy, or a cartilage repair procedure such as an osteochondral allograft transplantation or matrix-associated autologous chondrocyte implantation. Results: A total of 50 patients were surveyed (mean age: 53 years). The patients’ average rating for likelihood to use autologous cells was 8.86 ± 2.2 out of 10 and the average rating for likelihood to use allogeneic cells was 6.24 ± 3.3; 46% of patients had no specific concerns about autologous cell therapy, while 28% expressed concerns about efficacy, and 12% had concerns about donor age. The top 2 “main concerns” about allogeneic cell therapy were disease transmission (30%) and immune reaction (24%). Conclusions: This survey found that patients asserted a preference for autologous cell therapy in orthopedics. Further research is necessary to further elucidate the factors related to cell therapy that are most important to patients.

Interim results of viagenpumatucel-L (HS-110) plus nivolumab in previously treated patients (pts) with advanced non-small cell lung cancer (NSCLC) in two treatment settings.

9100 Background: Viagenpumatucel-L (HS-110) is an allogeneic cell therapy derived from a human lung adenocarcinoma cell line incorporating multiple cancer testis antigens and transfected with a gp96-Ig fusion protein. Methods: We report interim results of cohort A (previously treated pts who had not received a checkpoint inhibitor [CPI]) and cohort B (pts who progressed after CPI treatment) in an ongoing phase 2 trial evaluating HS-110 plus nivolumab (NIVO) in advanced NSCLC pts (NCT02439450). Pts received HS-110 (1×107 cells) intradermally QW for 18 wk and NIVO Q2W until tumor progression. Stratified analyses were performed by injection site reaction (ISR), yes (+) or no (–); baseline blood tumor mutational burden (bTMB), bTMB-L (<10 mutations/ megabase [mut/Mb]) or bTMB-H (≥10 mut/Mb) by FoundationACT test; and baseline PD-L1 expression, – (<1%) or + (≥1%). Results: As shown in the Table, median progression-free survival (PFS) in cohort A (n=47) was 1.8 mo (95% CI 1.8-7.8) and median overall survival (OS) was 24.6 mo (95% CI 11.7-36.0) after a median follow-up (MFU) of 19.5 mo. We observed significantly longer PFS and OS in ISR+ pts (hazard ratio [HR] 0.43, p=0.01; HR 0.23, p<0.001) and longer OS in PD-L1+ pts (HR 0.25, p=0.02). In cohort B (n=68), median PFS was 2.8 mo (1.8-3.9) and median OS was 11.9 mo (9.7-16.3) after a MFU of 11.9 mo. We observed significantly longer OS in ISR+ pts (HR 0.48, p=0.03) and a trend toward extended OS in bTMB-L pts (HR 0.58, p=0.20). HS-110 TEAEs were reported in 21 (44.7%) pts in cohort A and 18 (26.5%) pts in cohort B. TEAEs in >5% of pts included fatigue, maculopapular rash, nausea, diarrhea, and pruritus. Few HS-110–related TEAEs led to discontinuation of treatment [cohort A, 5 (10.6%); cohort B, 3 (4.4%)], and no serious AEs were considered related to HS-110. Conclusions: HS-110 was well tolerated when administered in combination with NIVO. In previously treated pts with advanced NSCLC, we observed (1) significantly longer PFS and OS in ISR+ pts in both CPI naïve and CPI progressor cohorts; (2) significantly longer OS in PD-L1+ patients in the CPI naïve cohort; and (3) a trend of improved OS in bTMB-L pts in the CPI progressor cohort. Further clinical evaluation of HS-110 is warranted in both CPI naïve and CPI progressor NSCLC patients. Clinical trial information: NCT02439450. [Table: see text]

Rapid GMP-Compliant Expansion of SARS-CoV-2–Specific T Cells From Convalescent Donors for Use as an Allogeneic Cell Therapy for COVID-19

COVID-19 disease caused by the SARS-CoV-2 virus is characterized by dysregulation of effector T cells and accumulation of exhausted T cells. T cell responses to viruses can be corrected by adoptive cellular therapy using donor-derived virus-specific T cells. One approach is the establishment of banks of HLA-typed virus-specific T cells for rapid deployment to patients. Here we show that SARS-CoV-2–exposed blood donations contain CD4 and CD8 memory T cells which recognize SARS-CoV-2 spike, nucleocapsid and membrane antigens. Peptides of these antigens can be used to isolate virus-specific T cells in a GMP-compliant process. The isolated T cells can be rapidly expanded using GMP-compliant reagents for use as an allogeneic therapy. Memory and effector phenotypes are present in the selected virus-specific T cells, but our method rapidly expands the desirable central memory phenotype. A manufacturing yield ranging from 1010 to 1011 T cells can be obtained within 21 days culture. Thus, multiple therapeutic doses of virus-specific T cells can be rapidly generated from convalescent donors for potential treatment of COVID-19 patients.

110 In-depth characterization of variability in apheresis collections from normal donor populations for allogeneic cell therapy

BackgroundThe success of autologous CAR-T cell therapies has revolutionized and accelerated development in the cell therapy field. However, the requirement for patient-specific starting material for these therapies remains an impediment to establishing availability for all patients who could benefit, highlighting the need for a highly characterized normal donor pool to generate allogeneic cell therapy material.MethodsWe have established a network of >2800 normal donors that have been genotyped at the HLA loci (6 digits) and stratified by reactivity to common human viruses, such as cytomegalovirus (CMV) and Epstein Barr Virus (EBV). Furthermore, cell collections from 35 randomly selected donors have been screened by flow cytometry for major immune cell subsets, including T cells, B cells, NK cells, and monocytes. The T cell compartment was further characterized by expression of activation markers (CD25, PD1, CD69) and proliferative capacity in response to anti-CD3/CD28 stimulation.ResultsN/AAbstract 110 Table 1ConclusionsThere was substantial variability (%CV 14.52%-50.58%, see table 1) in the percentage of each immune cell population across the donor pool, which would have effects on the relative success of downstream cell manufacturing. We are evaluating additional donors to identify specific sources of variability. Collectively, these data highlight the need for in-depth genotypic and phenotypic characterization of donor populations to ensure that the most robust material is selected for each type of cell therapy manufacturing.

Rapid GMP-compliant expansion of SARS-CoV-2-specific T cells from convalescent donors for use as an allogeneic cell therapy for COVID-19

COVID-19 disease caused by the SARS-CoV-2 virus is characterized by dysregulation of effector T cells and accumulation of exhausted T cells. T cell responses to viruses can be corrected by adoptive cellular therapy using donor-derived virus-specific T cells. Here we show that SARS-CoV-2-exposed blood donations contain CD4 and CD8 memory T cells specific for SARS-CoV-2 spike, nucleocapsid and membrane antigens. These peptides can be used to isolate virus-specific T cells in a GMP-compliant process. These T cells can be rapidly expanded using GMP-compliant reagents for use as a therapeutic product. Memory and effector phenotypes are present in the selected virus-specific T cells, but our method rapidly expands the desirable central memory phenotype. A manufacturing yield ranging from 1010 to 1011 T cells can be obtained within 21 days culture. Thus, multiple therapeutic doses of virus-specific T cells can be rapidly generated from convalescent donors for treatment of COVID-19 patientsOne Sentence SummaryCD4+ and CD8+ T cells specific for SARS-CoV-2 can be isolated from convalescent donors and rapidly expanded to therapeutic doses at GMP standard, maintaining the desired central memory phenotype required for protective immune responses against severe COVID-19 infections.