Preparedness and response of assisted living facilities toward COVID-19 infection control in Houston, Texas, USA.

Background: Long-term care facilities (LTCFs) including assisted living facilities (ALFs) are hubs for high transmission and poor prognosis of COVID-19 among the residents who are more susceptible due to old age and comorbidities. Aim: Houston Health Department conducted assessments of ALFs within the City of Houston to determine preparedness and existing preventive measures at the facilities. Methods: Onsite assessments were conducted at ALFs using a modified CDC Infection Control Assessment and Response (ICAR) Tool. Data was obtained on IPC measures, training, testing, vaccination etc. Data was analyzed, frequencies generated, and bivariate associations determined. Results: A total of 118 facilities were assessed and categorized into small scale 46 (39%), medium scale 47 (40%), and large scale 25 (21%). The facilities had 2431 residents and 2290 staff. Thirty-one (26%) facilities reported an outbreak in 2020, while 14 (12%) had an ongoing outbreak. Twenty-three (97%) large-scale and 12 (26%) small-scale facilities had COVID-19 testing program. Vaccination coverage among residents ranged from 99% in large-scale to 40% in small-scale facilities but was smaller among staff at 748 (45%) in large scale, 71 (36%) in small scale, and 193 (45%) in medium scale. While 24 (96%) large-scale and 34 (77%) of small-scale facilities conducted staff training staff on IPC practices, 22 (92%) of large-scale and 19 (56%) of small-scale facility staff demonstrated capacity (p = 0.01), respectively. Visitor screening was done at 100% of large-scale and 80% of small-scale and the medium-scale ALFs. Discussion: Assisted living facilities within the city of Houston are at various levels of preparedness and interventions with respect to COVID-19 response.

Prospective Analysis of Adoptive TIL Therapy in Patients with Metastatic Melanoma: Response, Impact of Anti-CTLA4, and Biomarkers to Predict Clinical Outcome.

Purpose: Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) has consistently demonstrated clinical efficacy in metastatic melanoma. Recent widespread use of checkpoint blockade has shifted the treatment landscape, raising questions regarding impact of these therapies on response to TIL and appropriate immunotherapy sequence.Patients and Methods: Seventy-four metastatic melanoma patients were treated with autologous TIL and evaluated for clinical response according to irRC, overall survival, and progression-free survival. Immunologic factors associated with response were also evaluated.Results: Best overall response for the entire cohort was 42%; 47% in 43 checkpoint-naïve patients, 38% when patients were exposed to anti-CTLA4 alone (21 patients) and 33% if also exposed to anti-PD1 (9 patients) prior to TIL ACT. Median overall survival was 17.3 months; 24.6 months in CTLA4-naïve patients and 8.6 months in patients with prior CTLA4 blockade. The latter patients were infused with fewer TIL and experienced a shorter duration of response. Infusion of higher numbers of TIL with CD8 predominance and expression of BTLA correlated with improved response in anti-CTLA4 naïve patients, but not in anti-CTLA4 refractory patients. Baseline serum levels of IL9 predicted response to TIL ACT, while TIL persistence, tumor recognition, and mutation burden did not correlate with outcome.Conclusions: This study demonstrates the deleterious effects of prior exposure to anti-CTLA4 on TIL ACT response and shows that baseline IL9 levels can potentially serve as a predictive tool to select the appropriate sequence of immunotherapies. Clin Cancer Res; 24(18); 4416-28. ©2018 AACR.

Utilizing T-cell Activation Signals 1, 2, and 3 for Tumor-infiltrating Lymphocytes (TIL) Expansion: The Advantage Over the Sole Use of Interleukin-2 in Cutaneous and Uveal Melanoma.

In this study, we address one of the major critiques for tumor-infiltrating lymphocyte (TIL) therapy-the time needed for proper expansion of a suitable product. We postulated that T-cell receptor activation in the first phase of expansion combined with an agonistic stimulation of CD137/4-1BB and interleukin-2 would favor preferential expansion of CD8 TIL. Indeed, this novel 3-signal approach for optimal T-cell activation resulted in faster and more consistent expansion of CD8CD3 TIL. This new method allowed for successful expansion of TIL from cutaneous and uveal melanoma tumors in 100% of the cultures in <3 weeks. Finally, providing the 3 signals attributed to optimal T-cell activation led to expansion of TIL capable of recognizing their tumor counterpart in cutaneous and uveal melanoma. This new methodology for the initial phase of TIL expansion brings a new opportunity for translation of TIL therapy in challenging malignancies such as uveal melanoma.

Intrathecal Administration of Tumor-Infiltrating Lymphocytes Is Well Tolerated in a Patient with Leptomeningeal Disease from Metastatic Melanoma: A Case Report.

UNLABELLED: Patients with leptomeningeal disease (LMD) from melanoma have very poor outcomes and few treatment options. We present a case of intrathecal (i.t.) administration of autologous tumor-infiltrating lymphocytes (TIL) in a patient with LMD from metastatic melanoma. The patient developed LMD after previous treatments with surgery, high-dose bolus interleukin-2 (HD IL2), and systemic TIL infusion and experienced radiographic progression after intrathecal IL2 (i.t. IL2) therapy. The patient received weekly treatment with increasing numbers of i.t. TIL followed by twice-weekly i.t. IL2. The patient received three i.t. TIL infusions and did not experience any toxicities beyond those expected with i.t. IL2 therapy. Analysis of cerebrospinal fluid demonstrated increased inflammatory cytokines following the i.t. TREATMENTS: Subsequent imaging demonstrated disease stabilization, and neurological deficits also remained stable. The patient expired 5 months after the initiation of i.t. TIL therapy with disease progression in the brain, liver, lung, and peritoneal and retroperitoneal lymph nodes, but without LMD progression. These results demonstrate the safety of i.t. administration of TIL in melanoma patients with LMD and support the feasibility of conducting a prospective clinical trial to determine this therapy's clinical benefit among these patients.

Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients.

PURPOSE: Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) is a promising treatment for metastatic melanoma unresponsive to conventional therapies. We report here on the results of an ongoing phase II clinical trial testing the efficacy of ACT using TIL in patients with metastatic melanoma and the association of specific patient clinical characteristics and the phenotypic attributes of the infused TIL with clinical response. EXPERIMENTAL DESIGN: Altogether, 31 transiently lymphodepleted patients were treated with their expanded TIL, followed by two cycles of high-dose interleukin (IL)-2 therapy. The effects of patient clinical features and the phenotypes of the T cells infused on the clinical response were determined. RESULTS: Overall, 15 of 31 (48.4%) patients had an objective clinical response using immune-related response criteria (irRC) with 2 patients (6.5%) having a complete response. Progression-free survival of more than 12 months was observed for 9 of 15 (60%) of the responding patients. Factors significantly associated with the objective tumor regression included a higher number of TIL infused, a higher proportion of CD8(+) T cells in the infusion product, a more differentiated effector phenotype of the CD8(+) population, and a higher frequency of CD8(+) T cells coexpressing the negative costimulation molecule "B- and T-lymphocyte attenuator" (BTLA). No significant difference in the telomere lengths of TIL between responders and nonresponders was identified. CONCLUSION: These results indicate that the immunotherapy with expanded autologous TIL is capable of achieving durable clinical responses in patients with metastatic melanoma and that CD8(+) T cells in the infused TIL, particularly differentiated effectors cells and cells expressing BTLA, are associated with tumor regression.