No data regarding the efficacy of a third mRNA vaccine for solid cancer patients previously primed with the heterologous CoronoVac/ChAdOx1 vaccination implemented in Thailand during the shortage of vaccine supply are available. Forty-four cancer patients who previously received the heterologous CoronaVac-ChAdOx1 regimen were boosted with a third mRNA COVID vaccine, either BNT162b2 or mRNA-1273. Anti-RBD IgG was measured immediately before, two weeks after, and four weeks after the third dose. The antibody response was compared to 87 age- and gender-matched cancer patients who were primed with the homologous ChAdOx1/ChAdOx1 regimens. Post-third dose anti-RBD IgG levels significantly increased compared to pre-third dose levels. There was no statistical difference in post-third dose antibody titers or neutralization levels between these two primary series regimens. Treatment with chemotherapy was associated with a lower antibody response compared to endocrine therapy/biologics. Similar antibody levels were observed after a third booster with either BNT162b2 or mRNA-1273 following heterologous CoronaVac/ChAdOx1 vaccination. There was no statistical difference in the immune response following the third-dose vaccination between cancer patients and healthy individuals who received the same heterologous CoronaVac/ChAdOx1 vaccination. In conclusion, a similar degree of enhanced immunogenicity was observed after a third mRNA COVID-19 vaccination in solid cancer patients who previously received the heterologous CoronaVac/ChAdOx1 regimens.

Limited data exists regarding the efficacy of ChAdOx1-nCoV-19 vaccine against Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) in solid cancer patients. We aimed to assess the immunogenicity of the ChAdOx1-nCoV-19 vaccine and the impact of different anticancer therapies for solid malignancies on immune response. This prospective, longitudinal observational study of immunogenicity following ChAdOx1-nCoV-19 vaccination among 385 solid cancer patients on active cancer treatment was conducted in two oncology centers. Participants received the first dose between June 18 and July 27, 2021 and the second dose at 8-10 weeks later. Blood samples were evaluated for total immunoglobulins against the receptor-binding of SARS-CoV-2 spike protein (anti-RBD total-Ig) before, and 4-week after the first- and second-doses. The primary endpoint was the geometric mean titers (GMT) of antibody among solid cancer patients compared to healthy controls and the impact of different cancer treatment types. Among solid cancer patients, the antibody level increased more slowly to significantly lower levels than achieved in healthy controls. The GMT at 4-weeks post-vaccination in cancer vs. healthy were 224.5 U/ml (95%CI 176.4–285.6) vs. 877.1 U/ml (95%CI 763.5–1008), p<0.0001), respectively. For different types of cancer treatments, chemotherapy agents, especially anthracyclines (GMR 0.004; 95%CI 0.002–0.008), paclitaxel (GMR 0.268; 95%CI 0.123–0.581), oxaliplatin (GMR 0.340; 95%CI 0.165–0.484), and immunotherapy (GMR 0.203; 95%CI 0.109–0.381) showed significantly lower antibody response. Anti-HER2, endocrine therapy and 5-fluouracil or gemcitabine, however, had less impact on the immune response. Suboptimal and heterogeneous immunologic responses were observed in cancer patients being treated with different systemic treatments. Immunotherapy or chemotherapy significantly suppressed the antibody response. Quality Improvement Fund, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society and Center of Excellence in Clinical Virology at Chulalongkorn University and Chulalongkorn Medical Oncology Research Fund

Purpose The epidermal growth factor receptor (EGFR) mutation is a widely prevalent oncogene driver in non–small cell lung cancer (NSCLC) in East Asia. The detection of EGFR mutations is a standard biomarker test performed routinely in patients with NSCLC for the selection of targeted therapy. Here, our objective was to develop a portable new technique for detecting EGFR (19Del, T790M, and L858R) mutations based on Nanopore sequencing.Materials and Methods The assay employed a blocker displacement amplification (BDA)–based polymerase chain reaction (PCR) technique combined with Nanopore sequencing to detect EGFR mutations. Mutant and wild-type EGFR clones were generated from DNA from H1650 (19Del heterozygous) and H1975 (T790M and L858R heterozygous) lung cancer cell lines. Then, they were mixed to assess the performance of this technique for detecting low variant allele frequencies (VAFs). Subsequently, formalin-fixed, paraffin-embedded (FFPE) tissue and cell-free DNA (cfDNA) from patients with NSCLC were used for clinical validation.Results The assay can detect low VAF at 0.5% mutant mixed in wild-type EGFR. Using FFPE DNA, the concordance rates of EGFR 19Del, T790M, and L858R mutations between our method and Cobas real-time PCR were 98.46%, 100%, and 100%, respectively. For cfDNA, the concordance rates of EGFR 19Del, T790M, and L858R mutations between our method and droplet digital PCR were 94.74%, 100%, and 100%, respectively.Conclusion The BDA amplicon Nanopore sequencing is a highly accurate and sensitive method for the detection of EGFR mutations in clinical specimens.

There are limited data available about the durability of the immune response after administration of the widely used adenovirus-vectored ChAdOx1-nCoV-19 vaccine in cancer patients. This prospective longitudinal observational study analyzed follow-up data of immunogenic responses 12 weeks after the second dose of the ChAdOx1-nCoV-19 vaccine in 290 oncological patients compared to healthy controls. The study aimed to assess the persistence of the humoral immune response three months after the second dose, and omicron neutralization was also evaluated. Three months after completion of the second vaccine dose, the geometric mean titer of SARS-CoV-2 binding total Ig statistically decreased by 42% compared to those at 4 weeks, and was lower than that of the healthy control. Six percent of patients became seronegative for anti-RBD total Ig. Only 5% (2 of 40 samples) tested positive for surrogate neutralization against SAR-CoV-2 Omicron BA.2. Across different therapy types, a waning in immunogenicity was observed within three months after the second dose of the ChAdOx1 nCoV-19 vaccine, rendering it insufficient at that point to protect against the SAR-CoV-2 Omicron BA.2 variant.

Background/Objectives: Skin cancers belong to the most frequent cancer type with over a million cases per year. Presently, transdermal drug delivery systems (TDDS) are an attractive drug delivery route, but they still face some limitations due to the resistance of human skin. Methods: Here, Sonidegib, PEDOT:PSS, and gelatins were employed as the model drug, drug carrier, and drug matrix, respectively. Results: Gelatin hydrogels were fabricated via the physical crosslinking to avoid toxicity towards the human skin. PEDOT:PSS was synthesized by chemical oxidative polymerization as the drug carrier. Sonidegib first interacted with PEDOT:PSS before they were embedded into the gelatin hydrogels. In the release and release-permeation experiments, the amounts of Sonidegib released and permeated were investigated under the effects of gelatin types, concentrations, pH values, PEDOT:PSS, and electrical voltages. For the effect of gelatin types, the BG gelatin provided higher amounts of Sonidegib release than PG from the higher electrorepulsive force. Under applied electrical voltages and with PEDOT:PSS present, the amounts of Sonidegib release and release-permeation amounts increased as PEDOT:PSS assisted in providing higher electroosmosis and electrorepulsive forces. Conclusions: In summary, PEDOT:PSS in the BG hydrogel is demonstrated here as a potential drug carrier to improve the Sonidegib release and release-permeation iontophoretically for TDDS.

Purpose: To evaluate the safety and immunogenicity of intramuscularly delivered personalized neoantigen synthetic long peptide (SLP) vaccines in patients with advanced solid tumors. Patients and Methods: In this phase I trial, 12 patients with advanced melanoma (n = 9) or renal cell carcinoma (n = 3) who lacked access to further reimbursed standard therapies at enrollment received intramuscular neoantigen SLP vaccines with Polyinosinic-Polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC). Each vaccine contained about 20 predicted neoantigen peptides. Adverse events were monitored throughout vaccination and follow-up. Immune profiling was performed at baseline and predefined postvaccination time points. Results: Intramuscular neoantigen vaccination was well tolerated, with only grade 1 to 2 local pain or fever and no immune-mediated toxicities. All participants developed de novo T-cell responses, which were detectable as early as 1 week after vaccination in most patients. On average, 53% of peptides per patient were immunogenic, inducing both CD8+ and CD4+ neoantigen-specific responses. Patients previously treated with immune checkpoint inhibitors (ICI) had higher baseline immunity but achieved comparable postvaccination responses to ICI-naïve patients. IFNγ-dominant CD8+ and TNFα-dominant CD4+ responses were observed, along with increased effector memory differentiation. Two patients with higher CD8+ terminal effector memory RA (TEMRA) proportions were the longest survivors. Tumor biopsies revealed enhanced CD8+ infiltration, and epitope spreading occurred in two evaluable cases. An analysis of 239 peptides showed greater immunogenicity for dual MHC I/II–binding, cysteine-containing, in-frame insertions or deletions–derived or low variant allele frequency–derived mutations, whereas proline substitutions reduced responses. Conclusions: Intramuscular neoantigen SLP vaccination with poly-ICLC is safe and induces rapid, mutation-specific T-cell immunity with robust CD8+ effector responses. These findings support intramuscular administration as a promising strategy for peptide-based cancer vaccines.