Delayed Stent Infection after Deployment of a Carotid Dual Layer Stent in Dialysis Cases.

Objective: Infection after carotid artery stenting (CAS) is rare. We report two dialysis cases of delayed stent infection associated with a carotid dual-layer stent (DLS), which occurred several months after deployment of the stent. Case Presentations: Case 1: A 74-year-old man receiving dialysis underwent CAS with DLS. Three months after CAS, the patient developed a high fever, neck pain, and neck swelling. Neck CT and carotid ultrasonography (CUS) indicated an abscess around the inserted DLS. The patient was treated with antibiotic agents and fully recovered. Case 2: A 73-year-old man receiving dialysis underwent CAS with DLS. Two months after CAS, this patient also developed a high fever, neck pain, and neck swelling. Contrast-enhanced neck CT indicated inflammatory effusion with an abscess and a giant infectious pseudoaneurysm. Endovascular stent graft reconstruction was employed urgently under antibiotic therapy to prevent its rupture. However, intracranial hemorrhage occurred postoperatively and left hemiparesis remained. Conclusion: Delayed carotid stent infection is a rare but severe complication. The use of a DLS might be avoided during CAS for dialysis cases.

Impact of the coronavirus disease pandemic on robot-assisted radical prostatectomy and urologists' treatment behaviors: A single tertiary center retrospective study.

OBJECTIVES: To assess whether the coronavirus disease (COVID-19) pandemic affected the outcomes of robot-assisted radical prostatectomy (RARP) and urologists' treatment behaviors. METHODS: We retrospectively examined the medical records of 208 patients who had undergone RARP between August 2017 and December 2022. We compared the rate of preoperative androgen deprivation therapy (ADT), waiting period for RARP, patients' baseline characteristics and quality of life (QOL), proportion of adverse pathology on the RARP specimen, rate of Gleason grade group upgrading from biopsy to the RARP specimen, and prostate-specific antigen (PSA) recurrence-free survival between the pre-pandemic and pandemic groups. RESULTS: The rate of preoperative ADT was significantly higher during than before the COVID-19 pandemic (13.7% vs. 1.9%; p = 0.002). The baseline physical and mental QOL scores did not differ significantly between the groups. The proportion of D'Amico low-risk patients was significantly lower (13.6% vs. 1.2%, p = 0.005) and waiting period for RARP was significantly shorter (median 3.5 months vs. 4.0 months, p = 0.016) in the pandemic group than in the pre-pandemic group. There was no significant difference in the proportion of adverse pathology between the groups (p = 0.104); however, the upgrading rate was significantly higher in the pre-pandemic group (p = 0.002). There was no significant difference in PSA recurrence-free survival between the groups (log-rank, p = 0.752). CONCLUSIONS: The COVID-19 pandemic did not adversely affect the oncologic outcomes of RARP and QOL before RARP. However, it caused urologists to increase the use of preoperative ADT and to reserve RARP for higher-risk cases.

Usefulness of fluorescent ureteral catheter during laparoscopic residual ureterectomy.

Introduction: There have been reports of surgery for residual ureteral tumors, most of them involved open surgeries. Herein, we report a case of retroperitoneal scopic left ureteral resection and partial cystectomy, performed by placing a fluorescent ureteral catheter in the residual ureter. Case presentation: A 79-year-old man was admitted to our hospital with a chief complaint of gross hematuria. He had undergone transperitoneal left radical nephrectomy due to angiomyolipoma 20 years ago. Computed tomography and Magnetic resonance imaging revealed a solid tumor in the left residual ureter. Retroperitoneal scopic residual ureterectomy has been performed. During the operation, a fluorescent ureteral catheter proved to be very helpful in detecting the ureter. Conclusion: A fluorescent ureteral catheter is considered to be a useful tool in laparoscopic surgery, especially in cases where identification of the ureter is expected to be difficult, such as the residual ureter in this case.

International promotion of Japanese aging-related health services and products: Perspective of an international agency.

Asia is at a critical juncture of health development. The population is aging and shrinking. At the same time, the economy is developing rapidly. These two factors, which necessitate a new paradigm of health development: departing from dependence on Official Development Assistance (ODA) and transitioning towards a model with more involvement of industries (private sector), academia, and health care providers, the so-called public-private partnership (PPP) model. The Economic Research Institute for ASEAN and East Asia (ERIA) is studying the potential for broader application of the new concept for collaboration between Asian countries and Japan. In this article, the authors attempt to introduce the complete picture of a new health ecosystem advocated by Japan. We first look at the impacts of population aging and shrinking, followed by introducing two new approaches; regional and country-specific, with the involvement of ERIA. Then, the outcomes of the projects and Japanese technology, services and products relevant to the older population are introduced. Finally, based on the various projects and products, we focus more closely on the new health development model, the PPP model. We start from the theory and move to examine a tool for implementation, which is the formulation of a dialogue forum named the MEX (Medical Excellence X, where X can be substituted by the acronym of any participating country) project. The experience of these projects and case studies will benefit all ASEAN member countries and beyond. ERIA finds that the facilitation works of the Institute catalyze the progress. ERIA will remain committed to helping the endeavors initiated by Japan for the benefit of all.

State-of-the-Art Cancer Immunotherapies.

Cancer immunotherapy is a type of cancer therapy utilizing the immune system to fight against tumors [...].

Impact of frailty on cancer-related fatigue and quality of life in outpatients with prostate cancer: a cross-sectional study of patient-reported outcomes.

OBJECTIVE: To investigate the prevalence of frailty and its effects on cancer-related fatigue and quality of life among patients with prostate cancer. METHODS: In this cross-sectional study, questionnaires were administered to 254 outpatients who visited the Department of Urology at Kagawa University Hospital for prostate cancer; finally, 108 outpatients were analyzed. Frailty, cancer-related fatigue and quality of life were assessed using the G8 screening tool, Japanese version of the Brief Fatigue Inventory and Japanese version of the Short Form 8 Health Survey, respectively. We defined frailty based on a score ≤14 points and divided the patients into frailty and no-frailty groups. We also compared the severity of cancer-related fatigue and quality of life between groups. RESULTS: The prevalence of frailty among 108 outpatients was 63%. Older age correlated with frailty severity (P = 0.0007) but not cancer-related fatigue severity (P = 0.2391). The proportion of patients on treatment or with metastasis was not significantly different between groups. The frailty group had higher cancer-related fatigue severity (P = 0.004) and decreased levels of general activity, mood, walking ability, normal work and enjoyment of life, especially on the Brief Fatigue Inventory subscale. The frailty group had lower physical and mental quality of life than the no-frailty group or general population. CONCLUSIONS: The frailty rate for these patients increased with age, exceeding 60% regardless of the treatment status, and was associated with worsened cancer-related fatigue severity and reduced quality of life. Our study highlights the importance of assessing frailty when selecting treatment, especially in older patients.

Prognostication in Lymph Node-Positive Prostate Cancer with No PSA Persistence After Radical Prostatectomy.

BACKGROUND: This study aimed to create a prognostic model to predict disease recurrence among patients with lymph node involvement but no prostate-specific antigen (PSA) persistence and to explore its clinical utility. METHODS: The study analyzed patients with lymph node involvement after pelvic lymph node dissection with radical prostatectomy in whom no PSA persistence was observed between 2006 and 2019 at 33 institutions. Prognostic factors for recurrence-free survival (RFS) were analyzed by the Cox proportional hazards model. RESULTS: Among 231 patients, 127 experienced disease recurrence. The factors prognostic for RFS were PSA level at diagnosis (≥ 20 vs. < 20 ng/mL: hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.09-2.52; P = 0.017), International Society of Urological Pathology grade group at radical prostatectomy (RP) specimen (group ≥ 4 vs. ≤ 3: HR, 1.63; 95% CI 1.12-2.37; P = 0.010), pathologic T-stage (pT3b/4 vs. pT2/3a: HR, 1.70; 95% CI 1.20-2.42; P = 0.0031), and surgical margin status (positive vs. negative: HR, 1.60; 95% CI 1.13-2.28; P = 0.0086). The prognostic model using four parameters were associated with RFS and metastasis-free survival. CONCLUSION: The prognostic model in combination with postoperative PSA value and number of lymph nodes is clinically useful for discussing treatment choice with patients.

Peripheral neuropathy and nerve electrophysiological changes with enfortumab vedotin in patients with advanced urothelial carcinoma: a prospective multicenter cohort study.

BACKGROUND: Enfortumab vedotin is a novel antibody-drug conjugate used as a third-line therapy for the treatment of urothelial cancer. We aimed to elucidate the effect of enfortumab vedotin-related peripheral neuropathy on its efficacy and whether enfortumab vedotin-induced early electrophysiological changes could be associated with peripheral neuropathy onset. METHODS: Our prospective multicenter cohort study enrolled 34 patients with prior platinum-containing chemotherapy and programmed cell death protein 1/ligand 1 inhibitor-resistant advanced urothelial carcinoma and received enfortumab vedotin. The best overall response, progression-free survival, overall survival, and safety were assessed. Nerve conduction studies were also performed in 11 patients. RESULTS: The confirmed overall response rate and disease control rate were 52.9% and 73.5%, respectively. The median overall progression-free survival and overall survival were 6.9 and 13.5 months, respectively, during a median follow-up of 8.6 months. The patients with disease control had significantly longer treatment continuation and overall survival than did those with uncontrolled disease. Peripheral neuropathy occurred in 12.5% of the patients. The overall response and disease control rates were 83.3% and 100%, respectively: higher than those in patients without peripheral neuropathy (p = 0.028 and p = 0.029, respectively). Nerve conduction studies indicated that enfortumab vedotin reduced nerve conduction velocity more markedly in sensory nerves than in motor nerves and the lower limbs than in the upper limbs, with the sural nerve being the most affected in the patients who developed peripheral neuropathy (p = 0.011). CONCLUSION: Our results indicated the importance of focusing on enfortumab vedotin-induced neuropathy of the sural nerve to maximize efficacy and improve safety.

Preclinical evaluation of a novel CAR-T therapy utilizing a scFv antibody highly specific to MAGE-A4p230-239/HLA-A∗02:01 complex.

Despite the revolutionary success of chimeric antigen receptor (CAR)-T therapy for hematological malignancies, successful CAR-T therapies for solid tumors remain limited. One major obstacle is the scarcity of tumor-specific cell-surface molecules. One potential solution to overcome this barrier is to utilize antibodies that recognize peptide/major histocompatibility complex (MHCs) in a T cell receptor (TCR)-like fashion, allowing CAR-T cells to recognize intracellular tumor antigens. This study reports a highly specific single-chain variable fragment (scFv) antibody against the MAGE-A4p230-239/human leukocyte antigen (HLA)-A∗02:01 complex (MAGE-A4 pMHC), screened from a human scFv phage display library. Indeed, retroviral vectors encoding CAR, utilizing this scFv antibody as a recognition component, efficiently recognized and lysed MAGA-A4+ tumor cells in an HLA-A∗02:01-restricted manner. Additionally, the adoptive transfer of T cells modified by the CAR-containing glucocorticoid-induced tumor necrosis factor receptor (TNFR)-related receptor (GITR) intracellular domain (ICD), but not CD28 or 4-1BB ICD, significantly suppressed the growth of MAGE-A4+ HLA-A∗02:01+ tumors in an immunocompromised mouse model. Of note, a comprehensive analysis revealed that a broad range of amino acid sequences of the MAGE-A4p230-239 peptide were critical for the recognition of MAGE-A4 pMHC by these CAR-T cells, and no cross-reactivity to analogous peptides was observed. Thus, MAGE-A4-targeted CAR-T therapy using this scFv antibody may be a promising and safe treatment for solid tumors.

Electronic substituent effect on the conformation of a phenylalanine-incorporated cyclic peptide.

The Phe-incorporated cyclic peptide [cyclo(-Phe1-oxazoline2-d-Val3-thiazole4-Ile5-oxazoline6-d-Val7-thiazole8-)] is in a conformational equilibrium between square and folded forms in solution. In the folded form, a CH⋯π interaction between the Phe1 aromatic ring and the Oxz2 methyl group is observed. We endeavored to control the local conformation and thus modulate the CH⋯π interaction and flexibility of the Phe1 side chain by controlling the electronic substituent effects at the 4-position of the aromatic ring of the Phe1 residue. The effect of the 4-substituent on the global conformation was indicated by the linear relationship between the conformational free energies (ΔGo) determined through NMR-based quantification and the Hammett constants (σ). Electron-donating substituents, which had relatively strong CH⋯π interactions, promoted peptide folding by restraining the loss in entropy. Local control by the 4-substituent effects suggested that the Phe side chain exerts an entropic influence on the folding of these cyclic peptides.

Real-world prostate-specific antigen response and progression to castration-resistant prostate cancer among men with metastatic castration-sensitive prostate cancer treated with apalutamide: a multi-institutional study in the Chu-shikoku Japan Urological Consortium.

BACKGROUND: Japanese men receiving apalutamide often experience skin-adverse events (AEs), possibly requiring treatment interruption or dose reduction. However, concerns have arisen regarding the impact of these adjustments on the efficacy of apalutamide. Our study evaluated the efficacy, safety, and persistence of apalutamide in men with metastatic castration-sensitive prostate cancer (mCSPC). METHODS: We retrospectively reviewed the medical records of 108 men with mCSPC from 14 Japanese institutions. The primary outcomes were the efficacy of apalutamide: prostate-specific antigen (PSA) response (50%, 90% and < 0.2 decline) and progression to castration-resistant prostate cancer (CRPC). The secondary outcomes were the skin-AE and compliance of apalutamide. RESULTS: PSA50%, PSA90% and PSA < 0.2 declines were observed in 89.8, 84.3 and 65.7%, and the median time to CRPC progression was not reached. PSA < 0.2 decline and an initial full dose of apalutamide were significantly associated with a longer time to CRPC. The most common AE was skin-AE (50.9%), and there was no association between the occurrence of skin-AE and the time to CRPC (P = 0.72). The median apalutamide persistence was 29 months, which was longer in the initial full dose recipients than in the reduced dose recipients. The dosage is reduced in about 60% of patients within the first year of treatment in the initial full dose recipients. CONCLUSIONS: Our findings indicate the effectiveness of apalutamide in Japanese men with mCSPC, despite a substantial portion requiring dose reduction within a year among the initial full dose recipients.

Exhaustion, rather than lack of infiltration and persistence, of CAR-T cells hampers the efficacy of CAR-T therapy in an orthotopic PDAC xenograft model.

Chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated impressive success in the treatment of patients with hematologic tumors yet achieved very limited efficacy for solid tumors due to hurdles unique to solid tumors. It is also noted that the tumor microenvironment composition varies between tumor type, which again imposes unique set of hurdles in each solid tumor. Therefore, elucidation of individual hurdles is key to achieving successful CAR-T therapy for solid tumors. In the present study, we employed an orthotopic human PDAC xenograft model, in which quantitative, spatial and functional dynamics of CAR-T cells in tumor tissues were analyzed to obtain insights into ways of overcoming PDAC related hurdles. Contrary to previous studies that demonstrated a limited persistency and infiltration of CAR-T cells in many solid tumors, they persist and accumulated in PDAC tumor tissues. Ex vivo analysis revealed that CAR-T cells that had been recovered at different time points from mice bearing an orthotopic PDAC tumor exhibited a gradual loss of tumor reactivity. This loss of tumor reactivity of CAR-T cells was associated with the increased expression of AMP-activated protein kinase and Mitofusin 1/ Dynamin-related protein 1 ratio.

Impact of multiple H/D replacements on the physicochemical properties of flurbiprofen.

Although deuterium incorporation into pharmaceutical drugs is an attractive way to expand drug modalities, their physicochemical properties have not been sufficiently examined. This study focuses on examining the changes in physicochemical properties between flurbiprofen (FP) and flurbiprofen-d8 (FP-d8), which was successfully prepared by direct and multiple H/D exchange reactions at the eight aromatic C-H bonds of FP. Although the effect of deuterium incorporation was not observed between the crystal structures of FP and FP-d8, the melting point and heat of fusion of FP-d8 were lower than those of FP. Additionally, the solubility of FP-d8 increased by 2-fold compared to that of FP. Calculation of the interaction energy between FP/FP-d8 and water molecules using the multi-component density functional theory method resulted in increased solubility of FP-d8. These novel and valuable findings regarding the changes in physicochemical properties triggered by deuterium incorporation can contribute to the further development of deuterated drugs.

Sculpting Secondary Structure of a Cyclic Peptide: Conformational Analysis of a Cyclic Hexapeptide Containing a Combination of l-Leu, d-Leu, and Aib Residues.

We have previously reported that cyclo(l-Leu-d-Leu-Aib-l-Leu-d-Leu-Aib) (2), a cyclic hexapeptide consisting of heterochiral l-Leu and d-Leu (l-Leu-d-Leu) residues with achiral 2-aminoisobutyric acid (Aib) residues, forms a figure-8 conformation. In this study, we newly designed cyclo(l-Leu-d-Leu-Aib-d-Leu-l-Leu-Aib)+ (4), an epimer of 2, and examined the conformational differences between 2 and 4 by X-ray crystallographic analysis. Peptide 4 formed a planar cyclic conformation with an antiparallel ß-sheet hydrogen-bonding pattern. This investigation demonstrates the potential to manipulate the molecular conformation of cyclic peptides by simply arranging the l- and d-amino acids and emphasizes that diverse conformations can be obtained by using cyclic peptides. Harnessing cyclic peptides as platforms for distinct molecular structures is a promising approach to expanding the chemical space for various applications.

Efficacy and safety of second-line cabozantinib after immuno-oncology combination therapy for advanced renal cell carcinoma: Japanese multicenter retrospective study.

Immuno-oncology (IO) combination therapy is utilized as a first-line systemic treatment for advanced renal cell carcinoma. However, evidence supporting the use of cabozantinib after IO combination therapy is lacking. We retrospectively analyzed patients who received second-line cabozantinib after IO combination therapy using the Japanese Urological Oncology Group (JUOG) database. In total, 254 patients were enrolled in the JUOG global study, and 118 patients who received second-line cabozantinib comprised the study cohort. The objective response rate, disease control rate, second-line cabozantinib progression-free survival (PFS), and overall survival from second-line for overall were 32%, 75%, 10.5 months, and not reached, respectively, for first-line IO-IO therapy were 37%, 77%, 11.1 months, and not reached, respectively, versus 24%, 71%, 8.3 months, and not reached, respectively, for first-line IO-tyrosine kinase inhibitor therapy. In univariate and multivariate analyses, discontinuation of first-line treatment because of progressive disease and liver metastasis were independent risk factors for PFS. All-grade adverse events occurred in 72% of patients, and grade 3 or higher adverse events occurred in 28% of patients. Second line-cabozantinib after first-line IO combination therapy for advanced renal cell carcinoma was expected to be effective after either IO-IO or IO-TKI treatment and feasible in real-world practice.

Aggressive Prostate Cancer in Patients Treated with Active Surveillance.

Active surveillance has emerged as a promising approach for managing low-risk and favorable intermediate-risk prostate cancer (PC), with the aim of minimizing overtreatment and maintaining the quality of life. However, concerns remain about identifying "aggressive prostate cancer" within the active surveillance cohort, which refers to cancers with a higher potential for progression. Previous studies are predictors of aggressive PC during active surveillance. To address this, a personalized risk-based follow-up approach that integrates clinical data, biomarkers, and genetic factors using risk calculators was proposed. This approach enables an efficient risk assessment and the early detection of disease progression, minimizes unnecessary interventions, and improves patient management and outcomes. As active surveillance indications expand, the importance of identifying aggressive PC through a personalized risk-based follow-up is expected to increase.

αß-T cell receptor transduction gives superior mitochondrial function to γδ-T cells with promising persistence.

Adoptive cell therapy using allogeneic γδ-T cells is a promising option for off-the-shelf T cell products with a low risk of graft-versus-host disease (GVHD). Long-term persistence may boost the clinical development of γδ-T cell products. In this study, we found that genetically modified Vγ9+Vδ2+ T cells expressing a tumor antigen-specific αß-TCR and CD8 coreceptor (GMC) showed target-specific killing and excellent persistence. To determine the mechanisms underlying these promising effects, we investigated metabolic characteristics. Cytokine secretion by γδ-TCR-stimulated nongene-modified γδ-T cells (NGMCs) and αß-TCR-stimulated GMCs was equally suppressed by a glycolysis inhibitor, although the cytokine secretion of αß-TCR-stimulated GMCs was more strongly inhibited by ATP synthase inhibitors than that of γδ-TCR-stimulated NGMCs. Metabolomic and transcriptomic analyses, flow cytometry analysis using mitochondria-labeling dyes and extracellular flux analysis consistently suggest that αß-TCR-transduced γδ-T cells acquire superior mitochondrial function. In conclusion, αß-TCR-transduced γδ-T cells acquire superior mitochondrial function with promising persistence.

Incidental finding of extramammary Paget's disease during active surveillance for early-stage prostate cancer in a prostate biopsy.

Introduction: Skin tissue contamination within transcutaneous visceral organ biopsies is seldom found. We encountered a rare case of extramammary Paget's disease incidentally diagnosed by prostate biopsy during active surveillance for prostate cancer. Case presentation: A 71-year-old Japanese patient was diagnosed with prostate cancer, and active surveillance was selected. After 1 year, prostate biopsy was performed by a transperitoneal approach, and 16 biopsy cores were taken. One biopsy core contained skin tissue showing extramammary Paget's disease. Careful skin examination confirmed the presence of an extramammary Paget's disease lesion in the left perineum, and curative surgical resection was performed. Recurrence and metastasis did not occur after 6 months of follow-up. Conclusion: Although the perianal region is a common site of extramammary Paget's disease, early-stage extramammary Paget's disease is often asymptomatic. Thus, during a transcutaneous biopsy, it is important to consider the appearance of the skin and the pathological features of migrating skin tissue.

Oral 5-aminolevulinic acid administration before transurethral resection of bladder tumor induces perioperative nausea and vomiting.

BACKGROUND: The efficacy of photodynamic diagnosis using 5-aminolevulinic acid during transurethral resection of bladder tumors has been demonstrated, albeit with limited information regarding its side effects. This study aimed to clarify the impact of oral 5-aminolevulinic acid on perioperative nausea and vomiting (NV) for the first time in a real-world clinical practice setting. METHODS: Patients who underwent transurethral surgery at Kagawa University between April 2017 and March 2020 were included. Perioperative NV and antiemetic use status were prospectively assessed and compared between the patients who received oral 5-aminolevulinic acid and those who did not. Additionally, univariate and multivariate analyses were performed for predicting postoperative nausea and vomiting. RESULTS: Of 214 patients, 74 (34.6%) received oral 5-aminolevulinic acid preoperatively. The proportions of preoperative NV and antiemetic use in the patients who received 5-aminolevulinic acid were 9.5% and 4.1%, respectively, and higher than in those who did not (0% and 0%; P < 0.01 and P = 0.04, respectively). Postoperative NV (25.7%) and antiemetics use (8.0%) ratios in the patients who received 5-aminolevulinic acid were significantly different from those in the non-users group (3.6% and 2.1%, P < 0.01 and P < 0.01, respectively). Although no differences in risk factors were found for postoperative NV between the two groups, multivariate analyses indicated 5-aminolevulinic acid use as an independent predictive factor for postoperative NV (odds ratio, 11.5; 95% confidence interval, 3.98-33.3; P < 0.01). CONCLUSIONS: Our study clearly showed that oral administration of 5-aminolevulinic acid was associated with perioperative NV even without risk factors, highlighting the need for addressing its application.

CAR-Modified Vγ9Vδ2 T Cells Propagated Using a Novel Bisphosphonate Prodrug for Allogeneic Adoptive Immunotherapy.

The benefits of CAR-T therapy could be expanded to the treatment of solid tumors through the use of derived autologous αß T cell, but clinical trials of CAR-T therapy for patients with solid tumors have so far been disappointing. CAR-T therapy also faces hurdles due to the time and cost intensive preparation of CAR-T cell products derived from patients as such CAR-T cells are often poor in quality and low in quantity. These inadequacies may be mitigated through the use of third-party donor derived CAR-T cell products which have a potent anti-tumor function but a constrained GVHD property. Vγ9Vδ2 TCR have been shown to exhibit potent antitumor activity but not alloreactivity. Therefore, in this study, CAR-T cells were prepared from Vγ9Vδ2 T (CAR-γδ T) cells which were expanded by using a novel prodrug PTA. CAR-γδ T cells suppressed tumor growth in an antigen specific manner but only during a limited time window. Provision of GITR co-stimulation enhanced anti-tumor function of CAR-γδ T cells. Our present results indicate that, while further optimization of CAR-γδ T cells is necessary, the present results demonstrate that Vγ9Vδ2 T cells are potential source of 'off-the-shelf' CAR-T cell products for successful allogeneic adoptive immunotherapy.