Repeated photodynamic therapy mediates the abscopal effect through multiple innate and adaptive immune responses with and without immune checkpoint therapy.

In combination with immune checkpoint inhibitors, photodynamic therapy can induce robust immune responses capable of preventing local tumor recurrence and delaying the growth of distant, untreated disease (ie. the abscopal effect). Previously, we found that repeated photodynamic therapy (R-PDT) using porphyrin lipoprotein (PLP) as a photosensitizer, without the addition of an immune checkpoint inhibitor, can induce the abscopal effect. To understand why PLP mediated R-PDT alone can induce the abscopal effect, and how the addition of an immune checkpoint inhibitor can further strengthen the abscopal effect, we investigated the broader immune mechanisms facilitated by R-PDT and combination R-PDT + anti-PD-1 monoclonal antibody (αPD-1) in a highly aggressive, subcutaneous AE17-OVA mesothelioma dual tumor-bearing C57BL/6 mice. We found a 46.64-fold and 61.33-fold increase in interleukin-6 (IL-6) after R-PDT and combination R-PDT + αPD-1 relative to PBS respectively, suggesting broad innate immune activation. There was a greater propensity for antigen presentation in the spleen and distal, non-irradiated tumor draining lymph nodes, as dendritic cells and macrophages had increased expression of MHC class II, CD80, and CD86, after R-PDT and combination R-PDT + αPD-1. Concurrently, there was a shift in the proportions of CD4+ T cell subsets in the spleen, and an increase in the frequency of CD8+ T cells in the distal, non-irradiated tumor draining lymph nodes. While R-PDT had an acceptable safety profile, combination R-PDT + αPD-1 induced 1.26-fold higher serum potassium and 1.33-fold phosphorus, suggestive of mild laboratory tumor lysis syndrome. Histology revealed an absence of gross inflammation in critical organs after R-PDT and combination R-PDT + αPD-1 relative to PBS-treated mice. Taken together, our findings shed light on how the abscopal effect can be induced by PDT and strengthened by combination R-PDT + αPD-1, and suggests minimal toxicities after R-PDT.

Brain tumor patients and COVID-19 vaccines: results of an international survey.

Background: As the COVID-19 pandemic continues to unfold, the advent of multiple approved vaccines has led to a milestone in the fight against the virus. While vaccination rates and side effects are well established in the general population, these are largely unknown in patients with brain tumors. The purpose of this study was to determine if brain tumor patients and their caregivers have received a COVID-19 vaccine, and explore their thoughts and opinions on these vaccines. Methods: An anonymous 31-question online survey available in 8 languages was conducted from June 30, 2021 to August 31, 2021. The survey was open to adult brain tumor patients over the age of 18 and included both categorical and open-ended questions. Descriptive statistics and modified thematic analyses were performed for all questions as appropriate. Results: A total of 965 unique surveys were completed from 42 countries. The vast majority of both brain tumor patients and their caregivers have been vaccinated against COVID-19 (84.5% and 89.9%, respectively). No patient reported serious adverse events from any vaccine. Less than 10% of patients decided against receiving a vaccination against COVID-19, with the most common reason being concerns over the safety of the vaccine. Patients wanted more specific information on how COVID-19 vaccines might impact their future brain tumor treatment. Conclusions: In conclusion, the majority of brain tumor patients and their caregivers have received COVID-19 vaccines with no major side effects. Patients want more information on how COVID-19 vaccines might directly impact their brain tumor and future management.

Repeated porphyrin lipoprotein-based photodynamic therapy controls distant disease in mouse mesothelioma via the abscopal effect.

While photodynamic therapy (PDT) can induce acute inflammation in the irradiated tumor site, a sustained systemic, adaptive immune response is desirable, as it may control the growth of nonirradiated distant disease. Previously, we developed porphyrin lipoprotein (PLP), a ∼20 nm nanoparticle photosensitizer, and observed that it not only efficiently eradicated irradiated primary VX2 buccal carcinomas in rabbits, but also induced regression of nonirradiated metastases in a draining lymph node. We hypothesized that PLP-mediated PDT can induce an abscopal effect and we sought to investigate the immune mechanism underlying such a response in a highly aggressive, dual subcutaneous AE17-OVA+ mesothelioma model in C57BL/6 mice. Four cycles of PLP-mediated PDT was sufficient to delay the growth of a distal, nonirradiated tumor four-fold relative to controls. Serum cytokine analysis revealed high interleukin-6 levels, showing a 30-fold increase relative to phosphate-buffered solution (PBS) treated mice. Flow cytometry revealed an increase in CD4+ T cells and effector memory CD8+ T cells in non-irradiated tumors. Notably, PDT in combination with PD-1 antibody therapy prolonged survival compared to monotherapy and PBS. PLP-mediated PDT shows promise in generating a systemic immune response that can complement other treatments, improving prognoses for patients with metastatic cancers.

Brain tumors and COVID-19: the patient and caregiver experience.

BACKGROUND: Since the COVID-19 pandemic began, thousands of medical procedures and appointments have been canceled or delayed. The long-term effects of these drastic measures on brain tumor patients and caregivers are unknown. The purpose of this study is to better understand how COVID-19 has affected this vulnerable population on a global scale. METHODS: An online 79-question survey was developed by the International Brain Tumour Alliance, in conjunction with the SNO COVID-19 Task Force. The survey was sent to more than 120 brain tumor charities and not-for-profits worldwide and disseminated to pediatric and adult brain tumor patients and caregivers. Responses were collected from April to May 2020 and subdivided by patient versus caregiver and by geographical region. RESULTS: In total, 1989 participants completed the survey from 33 countries, including 1459 patients and 530 caregivers. There were no significant differences in COVID-19 testing rates (P = .662) or positive cases for brain tumor patients between regions (P = .1068). Caregivers were significantly more anxious than patients (P ≤ .0001). Patients from the Americas were most likely to have lost their jobs due to the pandemic, practiced self-isolation, and received telehealth services (P ≤ .0001). Patients from Europe experienced the most treatment delays (P = .0031). Healthcare providers, brain tumor charities, and not-for-profits were ranked as the most trusted sources of information. CONCLUSIONS: As a result of COVID-19, brain tumor patients and caregivers have experienced significant stress and anxiety. We must continue to provide accessible high-quality care, information, and support in the age of COVID-19.

Genetic modification of mouse effector and helper T lymphocytes expressing a chimeric antigen receptor.

Genetic modification of primary mouse T cells with chimeric antigen receptors (CAR) has emerged as an important tool for optimizing adoptive T cell immunotherapy strategies. However, limitations in current protocols for generating highly pure and sufficient numbers of enriched effector and helper CAR(+) T cell subsets remain problematic. Here, we describe a new retroviral transduction protocol for successfully generating transduced CD8(+) and CD4(+) T lymphocytes for in vitro and in vivo characterization.