Enhancement of the Abscopal Effect in Radiotherapy by In-situ Delivered CD40 Antibody: Pancreatic Adenocarcinoma Model

Metastasis is the cause of death in most cancers. It has been observed by Mole and others that radiotherapy at one site may lead to regression of metastatic cancer at other sites, which were not irradiated, this phenomenon is called ‘abscopal’ effect. Unfortunately, this regression is not predictable. Few studies observed some enhancement by systemic application of immunoadjuvants, which also has limited application because of generalized adverse effect. The purpose of this study is to evaluate the enhancing and abscopal effect of radiotherapy by in-situ delivered anti-CD40 in the treatment of pancreatic cancer. A syngeneic mouse model of pancreatic adenocarcinoma was generated in C57/BL6 background mouse using Panc02 cell lines in both flanks. The palpable sized tumors of left flanks were treated as four different randomized cohorts: control with no treatment, direct treatment with 5 Gy of radiation, intra tumor treatment with CD40 antibody, and in combination. Tumor growth was measured on both sides. Result shows that in-situ application of CD40 antibody significantly enhances the effect of radiotherapy. Reduction of tumor volume was observed in both sides. The treated tumors (left) show average of 75% reduction of tumor volume by combination treatment compare to 32% reduction by radiation alone. On the untreated side (right), it was 86% reduction with combination treatment compare to 20% reduction with the radiation alone which may be reminiscent of an abscopal effect. This result shows potential for translational studies to significantly extend the use of radiotherapy for the treatment of both localized and metastatic cancers

Nanoparticle Drones to Target Lung Cancer with Radiosensitizers and Cannabinoids

Nanotechnology has opened up a new, previously unimaginable world in cancer diagnosis and therapy, leading to the emergence of cancer nanomedicine and nanoparticle-aided radiotherapy. Smart nanomaterials (nanoparticle drones) can now be constructed with capability to precisely target cancer cells and be remotely activated with radiation to emit micrometer-range missile-like electrons to destroy the tumor cells. These nanoparticle drones can also be programmed to deliver therapeutic payloads to tumor sites to achieve optimal therapeutic efficacy. In this article, we examine the state-of-the-art and potential of nanoparticle drones in targeting lung cancer. Inhalation (INH) (air) versus traditional intravenous (“sea”) routes of navigating physiological barriers using such drones is assessed. Results and analysis suggest that INH route may offer more promise for targeting tumor cells with radiosensitizers and cannabinoids from the perspective of maximizing damage to lung tumors cells while minimizing any collateral damage or side effects

Radiation and Local Anti-CD40 Generate an Effective in situ Vaccine in Preclinical Models of Pancreatic Cancer

Radiation therapy induces immunogenic cell death, which can theoretically stimulate T cell priming and induction of tumor-specific memory T cell responses, serving as an in situ vaccine. In practice, this abscopal effect is rarely observed. We use two mouse models of pancreatic cancer to show that a single dose of stereotactic body radiation therapy (SBRT) synergizes with intratumoral injection of agonistic anti-CD40, resulting in regression of non-treated contralateral tumors and formation of long-term immunologic memory. Long-term survival was not observed when mice received multiple fractions of SBRT, or when TGFβ blockade was combined with SBRT. SBRT and anti-CD40 was so effective at augmenting T cell priming, that memory CD8 T cell responses to both tumor and self-antigens were induced, resulting in vitiligo in long-term survivors

Nanoparticle Drones to Target Lung Cancer with Radiosensitizers and Cannabinoids

Nanotechnology has opened up a new, previously unimaginable world in cancer diagnosis and therapy, leading to the emergence of cancer nanomedicine and nanoparticle-aided radiotherapy. Smart nanomaterials (nanoparticle drones) can now be constructed with capability to precisely target cancer cells and be remotely activated with radiation to emit micrometer-range missile-like electrons to destroy the tumor cells. These nanoparticle drones can also be programmed to deliver therapeutic payloads to tumor sites to achieve optimal therapeutic efficacy. In this article, we examine the state-of-the-art and potential of nanoparticle drones in targeting lung cancer. Inhalation (INH) (air) versus traditional intravenous (“sea”) routes of navigating physiological barriers using such drones is assessed. Results and analysis suggest that INH route may offer more promise for targeting tumor cells with radiosensitizers and cannabinoids from the perspective of maximizing damage to lung tumors cells while minimizing any collateral damage or side effects

Automated and robust beam data validation of a preconfigured ring gantry linear accelerator using a 1D tank with synchronized beam delivery and couch motions

PURPOSE: To develop an efficient and automated methodology for beam data validation for a preconfigured ring gantry linear accelerator using scripting and a one-dimensional (1D) tank with automated couch motions. MATERIALS AND METHODS: Using an application programming interface, a program was developed to allow the user to choose a set of beam data to validate with measurement. Once selected the program generates a set of instructions for radiation delivery with synchronized couch motions for the linear accelerator in the form of an extensible markup language (XML) file to be delivered on the ring gantry linear accelerator. The user then delivers these beams while measuring with the 1D tank and data logging electrometer. The program also automatically calculates this set of beams on the measurement geometry within the treatment planning system (TPS) and extracts the corresponding calculated dosimetric data for comparison to measurement. Once completed the program then returns a comparison of the measurement to the predicted result from the TPS to the user and prints a report. In this work lateral, longitudinal, and diagonal profiles were taken for fields sizes of 6 × 6, 8 × 8, 10 × 10, 20 × 20, and 28 × 28 cm RESULTS: Using this methodology, the TPS was validated to agree with measurement. All compared points yielded a gamma value less than 1 for a 1.5%/1.5 mm criteria (100% passing rate). Off axis profiles had \u3e98.5% of data points producing a gamma value \u3c1 with a 1%/1 mm criteria. All depth profiles produced 100% of data points with a gamma value \u3c1 with a 1%/1 mm criteria. All data points measured were within 1.5% or 2 mm distance to agreement. CONCLUSIONS: This methodology allows for an increase in automation in the beam data validation process. Leveraging the application program interface allows the user to use a single system to create the measurement files, predict the result, and then compare to actual measurement increasing efficiency and reducing the chance for user input errors

Erratum to: Investigation of the association between the TCF7L2 rs7903146 (C/T) gene polymorphism and obesity in a Cameroonian population: a pilot study

Upon publication of the original article [1], it was noticed that the author\u2019s name \u201cJean Jacques Noubiap\u201d was incorrectly given as \u201cJean Jacques N. Noubiap\u201d. This has now been acknowledged and corrected in this erratum

Investigation of the association between the TCF7L2 rs7903146 (C/T) gene polymorphism and obesity in a Cameroonian population: a pilot study

Objective: This study aimed at investigating the association between the rs7903146 (C/T) polymorphism of the TCF7L2 gene with obesity in a Cameroonian population. Method: This was a case-control pilot study including 61 obese and 61 non-obese Cameroonian adults. Anthropometric indices of obesity, blood pressure, fasting blood glucose, and blood lipids were measured. The rs7903146 (C/T) polymorphism of the TCF7L2 gene was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and genotypes were correlated with clinical and biological parameters. Results: The T allele was predominant in the study population with a frequency of 93%. No statistically significant difference was however observed between the genotypic (p = 0.50) and allelic frequencies (p = 0.58) of obese and non-obese subjects. Comparison of clinical and biochemical parameters of C allele carriers (CX = CC + CT) with those of TT genotype showed that there was no significant difference between the lipid profile of these two groups. Conclusion: The rs7903146 (C/T) polymorphism of the TCF7L2 gene might not be associated with obesity in the Cameroonian population

Priming the Abscopal Effect Using Multifunctional Smart Radiotherapy Biomaterials Loaded with Immunoadjuvants

In this study, we investigate the use of multifunctional smart radiotherapy biomaterials (SRBs) loaded with immunoadjuvants for boosting the abscopal effect of local radiotherapy (RT). SRBs were designed similar to currently used inert RT biomaterials, incorporating a biodegradable polymer with reservoir for loading payloads of the immunoadjuvant anti-CD40 monoclonal antibody. Lung (LLC1) tumors were generated both on the right and left flank of each mouse, with the left tumor representing metastasis. The mice were randomized and divided into eight cohorts with four cohorts receiving image-guided RT (IGRT) at 5 Gy and another similar four cohorts at 0 Gy. IGRT and Computed Tomography (CT) imaging were performed using a small animal radiation research platform (SARRP). Tumor volume measurements for both flank tumors and animal survival was assessed over 25 weeks. Tumor volume measurements showed significantly enhanced inhibition in growth for the right flank tumors of mice in the cohort treated with SRBs loaded with CD40 mAbs and IGRT. Results also suggest that the use of polymeric SRBs with CD40 mAbs without RT could generate an immune response, consistent with previous studies showing such response when using anti-CD40. Overall, 60% of mice treated with SRBs showed complete tumor regression during the observation period, compared to 10% for cohorts administered with anti-CD40 mAbs, but no SRB. Complete tumor regression was not observed in any other cohorts. The findings justify more studies varying RT doses and quantifying the immune-cell populations involved when using SRBs. Such SRBs could be developed to replace currently used RT biomaterials, allowing not only for geometric accuracy during RT, but also for extending RT to the treatment of metastatic lesions

Enhancing the Therapeutic Efficacy of Cancer Treatment With Cannabinoids

Over the years, many in vitro and in vivo studies have shown the antineoplastic effects of cannabinoids (CBDs), with reports advocating for investigations of combination therapy approaches that could better leverage these effects in clinical translation. This study explores the potential of combination approaches employing CBDs with radiotherapy (RT) or smart biomaterials toward enhancing therapeutic efficacy during treatment of pancreatic and lung cancers. In in vitro studies, clonogenic assay results showed greater effective tumor cell killing, when combining CBDs and RT. Meanwhile, in vivo study results revealed major increase in survival when employing smart biomaterials for sustained delivery of CBDs to tumor cells. The significance of these findings, considerations for further research, and viable roadmap to clinical translation are discussed