Long-term observation of antibody titers against SARS-CoV-2 following vaccination.

Objectives: We aimed to understand how SARS-CoV-2 antibody titer decrease following SARS-CoV-2 mRNA vaccination and to estimate the timing of booster vaccination. Study design: Six hundred sixty-two healthcare workers were administered with total of three doses of SARS-CoV-2 mRNA vaccine during the same short period. Of them, three volunteers were enrolled to measure anti-receptor binding domain (RBD) antibody titers (IgG) monthly following the second and the third doses. Methods: Serum anti-RBD antibody titers were measured monthly and the decay curve of the antibody was analyzed. We estimate the timing of the third and fourth vaccine based on the observed antibody titer decrease and the period of breakthrough infections in the vaccine recipients. Results: Anti-RBD antibody decreased exponentially following the 2nd dose. Between 108 and 117 days following the second dose, breakthrough infection of SARS-CoV-2 occurred in 11 out of the 662 vaccine recipients. Based on the decrease in anti-RBD antibody and the timing of the breakthrough infections, we estimate that the optimal timing of a third dose would be at earliest 108 days after the second dose, when anti-RBD antibody titers are less than 338 BAU/mL. The anti-RBD antibody titers were sustained relatively higher for 161 days following the third dose (416 days following the second dose). Conclusions: We estimate that the optimal timing of a third dose would be at earliest 108 days after the second dose, or anti-RBD antibody titers are less than 338 BAU/mL. We suggest that a fourth dose should be administered later than 161 days following the third dose.

Carney complex: a case with thyroid follicular adenoma without a PRKAR1A mutation.

BACKGROUND: Carney complex (CNC) is a very rare disease. Although thyroid lesions are included in the diagnostic criteria for CNC, they are an infrequent occurrence. CASE PRESENTATION: The patient was a 69-year-old woman who had undergone the removal of a left atrial myxoma 10 years earlier, at the age of 59. At the time of the operation, thyroid ultrasonography (US) revealed multiple hypoechoic nodules. Thyroid scintigraphy revealed an increased uptake of 99mTc in these lesions, which was consistent with toxic multinodular goiter, and she was diagnosed with CNC. Genetic studies showed no mutation in the PRKAR1A (protein kinase A regulatory subunit 1-α) gene. From then on, she received annual brain magnetic resonance imaging (MRI), abdominal computed tomography (CT), and thyroid US examinations. Her follicular thyroid nodules gradually increased in number and size. Although aspiration cytology samples from the thyroid nodules diagnosed them as class III, thyroid cancer could not be ruled out. The patient underwent a partial thyroidectomy, and the pathological diagnosis was multiple follicular adenomas. CONCLUSION: Careful and frequent evaluation of the thyroid gland should be required for CNC patients due to the potential for carcinoma to develop in the context of a variety of follicular thyroid lesions.

Prognostic value of HLA class I expression in patients with colorectal cancer.

BACKGROUND: Prognostic factors are useful for determination of the therapeutic strategy and follow-up examination after curative operation in cancer treatment. The immunological state of the host can influence the prognosis for cancer patients as well as the features of the cancer. Human lymphocyte antigen (HLA) class I molecules have a central role in the anti-cancer immune system. Therefore, we focused on the HLA class I expression level in cancer cells to investigate its prognostic value in patients with colorectal cancer. METHODS: We reviewed the clinical pathology archives of 97 consecutive patients with stage II colorectal cancer who underwent curative operation at the Sapporo Medical University, Japan, from February 1994 to January 2005. Fifty-six high-risk patients had adjuvant chemotherapy. The cancer cell membrane immunoreactivity level for HLA class I expressed by EMR8-5 was classified into three categories (positive, dull, and negative). In this study, the cases were divided into two groups: "positive" and "dull/negative". HLA class I expression level and clinicopathological parameters were evaluated with the Pearson χ (2) test. Survival analysis was assessed by the Kaplan-Meier methods, and the differences between survival curves were analyzed using the log-rank test. RESULTS: Immunohistochemical study of HLA class I revealed the following. There were 51 cases that were positive, 40 were dull, and six negative. The HLA class I expression level had no significant correlation with other clinicopathological parameters, except for gender. Univariate and multivariate analyses related to disease-free survival (DFS) revealed that tumor location, HLA expression level, and venous invasion were significant independent prognostic factors (P < 0.05). The 5-year DFS rates in HLA class I positive group and in the dull/negative group were 89% and 70%, respectively. For high-risk patients with adjuvant chemotherapy, the 5-year DFS rates in the HLA class I positive group and in the dull/negative group were 84% and 68%, respectively. For low-risk patients without the chemotherapy, the 5-year DFS rates in the HLA class I positive group and in the dull/negative group were 100% and 71%, respectively. CONCLUSIONS: Our study concluded that the HLA class I expression level might be a very sensitive prognostic factor in colorectal cancer patients with stage II disease.

Clinical and immunological evaluation of anti-apoptosis protein, survivin-derived peptide vaccine in phase I clinical study for patients with advanced or recurrent breast cancer.

BACKGROUND: We previously reported that survivin-2B, a splicing variant of survivin, was expressed in various types of tumors and that survivin-2B peptide might serve as a potent immunogenic cancer vaccine. The objective of this study was to examine the toxicity of and to clinically and immunologically evaluate survivin-2B peptide in a phase I clinical study for patients with advanced or recurrent breast cancer. METHODS: We set up two protocols. In the first protocol, 10 patients were vaccinated with escalating doses (0.1-1.0 mg) of survivin-2B peptide alone 4 times every 2 weeks. In the second protocol, 4 patients were vaccinated with the peptide at a dose of 1.0 mg mixed with IFA 4 times every 2 weeks. RESULTS: In the first protocol, no adverse events were observed during or after vaccination. In the second protocol, two patients had induration at the injection site. One patient had general malaise (grade 1), and another had general malaise (grade 1) and fever (grade 1). Peptide vaccination was well tolerated in all patients. In the first protocol, tumor marker levels increased in 8 patients, slightly decreased in 1 patient and were within the normal range during this clinical trial in 1 patient. With regard to tumor size, two patients were considered to have stable disease (SD). Immunologically, in 3 of the 10 patients (30%), an increase of the peptide-specific CTL frequency was detected. In the second protocol, an increase of the peptide-specific CTL frequency was detected in all 4 patients (100%), although there were no significant beneficial clinical responses. ELISPOT assay showed peptide-specific IFN-gamma responses in 2 patients in whom the peptide-specific CTL frequency in tetramer staining also was increased in both protocols. CONCLUSION: This phase I clinical study revealed that survivin-2B peptide vaccination was well tolerated. The vaccination with survivin-2B peptide mixed with IFA increased the frequency of peptide-specific CTL more effectively than vaccination with the peptide alone, although neither vaccination could induce efficient clinical responses. Considering the above, the addition of another effectual adjuvant such as a cytokine, heat shock protein, etc. to the vaccination with survivin-2B peptide mixed with IFA might induce improved immunological and clinical responses.

[Successful combination therapy with 5'-DFUR and MPA for breast cancer with spinal and vertebral metastases].

We report a case of breast cancer with spinal and vertebral lesions. A 49-year-old premenopausal woman with a left breast tumor was admitted to our hospital for acute weakness of the lower limbs and dysuria. She could neither stand nor walk. The tumor in the left breast was 5.0 cm in diameter with skin ulcer, and it was diagnosed as breast cancer. Magnetic resonance (MR) image showed multiple vertebral and spinal metastases from breast cancer. Chemotherapy, consisting of cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) was initiated. Her symptoms dramatically changed for the better. She became able to walk and urinate. We performed palliative mastectomy after 3 cycles of CAF therapy. Histopathological findings of breast tumor showed scirrhous carcinoma. Although the estrogen and progesterone receptor status of primary tumor was negative, chemo-endocrine therapy, consisting of medroxyprogesterone acetate (MPA) and doxifluridine (5'-DFUR) was given as daily therapy, and vertebral and spinal lesions were reduced. Her condition has remained stable for 4 years. For patients with metastatic breast cancer, complete remission is uncommon, and disease stabilization is a reasonable goal of successful therapy. In this respect, therapy with CAF, followed by MPA and 5'-DFUR, was successful in the patient.