Persistence of spike-specific immune responses in BNT162b2-vaccinated donors and generation of rapid ex-vivo T cells expansion protocol for adoptive immunotherapy: A pilot study.

Introduction: The BNT162b2 mRNA-based vaccine has shown high efficacy in preventing COVID-19 infection but there are limited data on the types and persistence of the humoral and T cell responses to such a vaccine. Methods: Here, we dissect the vaccine-induced humoral and cellular responses in a cohort of six healthy recipients of two doses of this vaccine. Results and discussion: Overall, there was heterogeneity in the spike-specific humoral and cellular responses among vaccinated individuals. Interestingly, we demonstrated that anti-spike antibody levels detected by a novel simple automated assay (Jess) were strongly correlated (r=0.863, P<0.0001) with neutralizing activity; thus, providing a potential surrogate for neutralizing cell-based assays. The spike-specific T cell response was measured with a newly modified T-spot assay in which the high-homology peptide-sequences cross-reactive with other coronaviruses were removed. This response was induced in 4/6 participants after the first dose, and all six participants after the second dose, and remained detectable in 4/6 participants five months post-vaccination. We have also shown for the first time, that BNT162b2 vaccine enhanced T cell responses also against known human common viruses. In addition, we demonstrated the efficacy of a rapid ex-vivo T cell expansion protocol for spike-specific T cell expansion to be potentially used for adoptive-cell therapy in severe COVID-19, immunocompromised individuals, and other high-risk groups. There was a 9 to 13.7-fold increase in the number of expanded T cells with a significant increase of anti-spike specific response showing higher frequencies of both activation and cytotoxic markers. Interestingly, effector memory T cells were dominant in all four participants' CD8+ expanded memory T cells; CD4+ T cells were dominated by effector memory in 2/4 participants and by central memory in the remaining two participants. Moreover, we found that high frequencies of CD4+ terminally differentiated memory T cells were associated with a greater reduction of spike-specific activated CD4+ T cells. Finally, we showed that participants who had a CD4+ central memory T cell dominance expressed a high CD69 activation marker in the CD4+ activated T cells.

Favorable Response to Treatment with Avelumab in an HIV-Positive Patient with Advanced Merkel Cell Carcinoma Previously Refractory to Chemotherapy.

Avelumab is indicated for the management of Merkel cell carcinoma, a rare and aggressive neuroendocrine skin cancer. Its regulatory approval followed the positive outcome of a Phase 2 trial on 88 patients with stage IV disease, which excluded patients with immunodeficiency due to HIV, a risk factor for this cancer type. We report a positive and sustained response to avelumab in an HIV-positive patient with stage IV Merkel cell carcinoma refractory to previous chemotherapy (cisplatin/etoposide) and radiotherapy. Five cycles of avelumab 10 mg/m2 resulted in the resolution of tumor activity visualized using PET-CT scanning in all affected lymph nodes. The only major side effect associated with avelumab was thyroiditis and mild hypothyroidism, a known adverse effect of this treatment, which was well controlled by L-thyroxine treatment. Treatment is ongoing and the positive response has been sustained during 5 further cycles of treatment up to date. This apparently durable response is consistent with the earlier clinical trial experience with avelumab, but seen here in a patient with HIV-associated immunodeficiency as a predisposing factor (an exclusion criterion from the previous trial). Further clinical trials with avelumab in a broader patient population with Merkel cell carcinoma are warranted.

Study of HER2/neu status in Qatari women with breast carcinoma.

OBJECTIVE: The study is aimed at determining the prevalence of HER2/neu overexpression in Qatari women with breast cancer and to assess the survival in patients with HER2/neu positive tumors. METHODS: This is a retrospective study of clinical data of 70 Qatari female patients diagnosed with breast cancer during the period 1991 through to 2001, at Hamad Medical Corporation, Doha, Qatar. We also performed a retrospective review of breast tissue sample for those patients using paraffin sections and applying immunohistochemistry staining-[Hercep test (DAKO Inc)] to determine the HER2/neu status. RESULTS: Eighteen patients (26%) were HER2/neu positive (2+ and 3+) with a mean age at diagnosis of 49.3years, and 52 (74%) were negative (0 and 1+) with mean age at diagnosis of 46.6 years. Of the patients with positive HER2/neu, 5 (28%) had a relapse of the disease and 4 (22%) died of the disease during follow up. Of the patients with HER2/neu, negative test 9 (17%) had a relapse of the disease and 10 (19%) died of the disease. The median survival function at mean of covariates for HER2/neu positive patients was 26 months, and for HER2/NEU negative patients was 28 months. CONCLUSION: The prevalence of HER2/neu over expression in Qatari female with breast cancer in this study is 26%, but due to a small sample size it may not reflect really the prevalence. Patient with HER2/neu positive were older at diagnosis than patients with HER2/neu negative, also they had higher relapse rate and mortality. Median survival function was better for HER2/neu negative patients.