SARS-CoV-2 vaccination elicits unconventional IgM specific responses in naïve and previously COVID-19-infected individuals

 Currently, evaluation of the IgG antibodies specific for the SARS-CoV-2 Spike protein following vaccination is used worldwide to estimate vaccine response. Limited data are available on vaccine-elicited IgM antibodies and their potential implication in immunity to SARS-CoV-2.
 We Bio Med Frontiers performed a longitudinal study to quantify anti-S SARS-CoV-2 IgG and IgM (IgG-S and IgM-S) in health care worker (HCW) recipients of the BNT162b2 vaccine.
Samples were collected before administration (T0), at the second dose (T1) and three weeks after T1 (T2). The cohort included 1584 immunologically naïve to SARS-CoV-2 (IN) and 289 with a history of previous infection (PI).
IN showed three patterns of responses: (a) IgG positive/IgM negative (36.1%), (b) coordinated IgM-S/IgG-S responses appearing at T1 (37.4%) and (c) IgM appearing after IgG (26.3%).
Coordinated IgM-S/IgG-S responses were associated with higher IgG titres. In IgM-S positive PI, 64.5% were IgM-S positive before vaccination, whereas 32% and 3.5% developed IgM-S after the first and second vaccine dose, respectively. IgM-S positive sera had higher pseudovirus neutralization titres compared to the IgM-S negative.
Coordinated expression of IgG-S and IgM-S after vaccination was associated with a significantly more efficient response in both antibody levels and virus-neutralizing activity. The unconventional IgG-S positive/IgM-S negative responses may suggest recruitment of cross coronaviruses immunity by vaccination, warranting further investigation.
 Italian Ministry of Health under “Fondi Ricerca Corrente”- L1P5 and “Progetto Ricerca Finalizzata COVID-2020-12371675”; FUR 2020 Department of Excellence 2018-2022, MIUR, Italy; The Brain Research Foundation Verona.

A CAR T-inspiring platform based on antibody-engineered exosomes from antigen-feeding dendritic cells for precise solid tumor therapy.

Chimeric antigen receptor T (CAR T) cell therapy has achieved remarkable results treating patients with hematological malignancies in clinical studies. Although promising, extensive research has also revealed that CAR T therapy is unsatisfactory for the treatment of solid tumors. In addition, the production of CAR T cells is time-consuming and it’s hard for storage and transportation. Antibodies
In this work, inspired by the construction of CAR T cell, we developed an antibody-engineered exosomes from antigen-feeding dendritic cells for beyond CAR T therapy of solid tumors by in situ T cells activation and cancer cell targeting.
We have confirmed that tumor antigen-stimulated dendritic cell-derived exosomes (tDC-Exo) provided major histocompatibility (MHC)-antigen complexes and CD86 co-stimulating molecules, which were the same as CAR of CAR T cell acting as the necessary signals for T cell activation.
Furthermore, anti-CD3 and anti-EGFR were then engineered on tDC-Exo to promote the binding of T cell to cancer cells for precise therapy. Our CAR T cell therapy-mimicking system have shown an efficient endogenous T cells activation and their crosslinking with cancer cells for enhanced solid tumor therapy.
More interestingly, we found that immune activation significantly up-regulated PD-L1 expression, and thus we confirmed the combination with anti-PD-L1 antibodies further enhanced the efficacy of our CAR T cell therapy-mimicking platform.

RNA-mediated immunotherapy regulating tumor immune microenvironment: next wave of cancer therapeutics.

  1. Accumulating research suggests that the tumor immune microenvironment (TIME) plays an essential role in regulation of tumor growth and metastasis. The cellular and molecular nature of the TIME influences cancer progression and metastasis by altering the ratio of immune- suppressive versus cytotoxic responses in the vicinity of the tumor.
  2. Targeting or activating the TIME components show a promising therapeutic avenue to combat cancer. The success of immunotherapy is both astounding and unsatisfactory in the clinic. Advancements in RNA-based technology have improved understanding of the complexity and diversity of the TIME and its effects on therapy.
  3. TIME-related RNA or RNA regulators could be promising targets for anticancer immunotherapy. In this review, we discuss the available RNA-based cancer immunotherapies targeting the TIME. More importantly, we summarize the potential of various RNA-based therapeutics clinically available for cancer treatment. RNA-dependent targeting of the TIME, as monotherapy or combined with other evolving therapeutics, might be beneficial for cancer patients’ treatment in the near future.

Role of Myostatin in Muscle Degeneration by Random Positioning Machine Exposure: An in vitro Study for the Treatment of Sarcopenia

  • Several scientific evidence have shown that exposure to microgravity has a significant impact on the health of the musculoskeletal system by altering the expression of proteins and molecules involved in bone-muscle crosstalk, which is also observed in the research of microgravity effect simulation.
  • Among these, the expression pattern of myostatin appears to play a key role in both load-free muscle damage and the progression of age-related musculoskeletal disorders, such as osteoporosis and sarcopenia.
  • Based on this evidence, we here investigated the efficacy of treatment with anti-myostatin (anti-MSTN) antibodies on primary cultures of human satellite cells exposed to 72 h of random positioning machine (RPM). Cell cultures were obtained from muscle biopsies taken from a total of 30 patients (controls, osteoarthritic, and osteoporotic) during hip arthroplasty.
  • The Pax7 expression by immunofluorescence was carried out for the characterization of satellite cells. We then performed morphological evaluation by light microscopy and immunocytochemical analysis to assess myostatin expression.
  • Our results showed that prolonged RPM exposure not only caused satellite cell death, but also induced changes in myostatin expression levels with group-dependent variations.
  • Surprisingly, we observed that the use of anti-MSTN antibodies induced a significant increase in cell survival after RPM exposure under all experimental conditions.
  • Noteworthy, we found that the negative effect of RPM exposure was counteracted by treatment with anti-MSTN antibodies, which allowed the formation of numerous myotubes. Our results highlight the role of myostatin as a major effector of the cellular degeneration observed with RPM exposure, suggesting it as a potential therapeutic target to slow the muscle mass loss that occurs in the absence of loading.

Transcriptome Analysis of Peripheral Blood Mononuclear Cells in SARS-CoV-2 Naïve and Recovered Individuals Vaccinated With Inactivated Vaccine.

The urgent approval of the use of the inactivated COVID-19 vaccine is essential to reduce the threat and burden of the epidemic on global public health, however, our current understanding of the host immune response to inactivated vaccine remains limited.
Herein, we performed serum IgG antibody detection and transcriptomics analysis on 20 SARS-CoV-2 naïve individuals who received multiple doses of inactivated vaccine and 5 SARS-CoV-2 recovered individuals who received single dose of inactivated vaccine.
Our research revealed the important role of many innate immune pathways after vaccination, identified a significant correlation with the third dose of booster vaccine and proteasome-related genes, and found that SARS-CoV-2 recovered individuals can produce a strong immune response to a single dose of inactivated vaccine.
These results help us understand the reaction mechanism of the host’s molecular immune system to the inactivated vaccine, and provide a basis for the choice of a vaccination strategy.

Management of relapsed or refractory large B-cell lymphoma in patients ineligible for CAR-T cell therapy.

 Chimeric antigen receptor T (CAR-T) therapy has revolutionized the treatment of relapsed/refractory large B-cell lymphoma (LBCL).
However, patients who are excluded or have no access to CAR-T represent a challenge for clinicians and have generally a dismal outcome. The landscape for this category of patients is constantly evolving: new agents have been approved in the last 2-3 years, alone or in combination, and novel treatment modalities are under investigations.
 Thereafter, we reviewed the currently available therapeutic strategies: conventional chemotherapy, Antibody-drug conjugate ADC (mainly polatuzumab and loncastuxumab), bispecific antibodies (CD19/CD3 and focus on novel CD20/CD3 Abs), immunomodulatory drugs (covering tafasitamab and lenalidomide, checkpoint inhibitors mainly in PMBL), small molecules (selinexor, BTK and PI3K inhibitors), and the role of radiotherapy.

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 Navigating this scenario will uncover new challenges, including identifying an ideal sequence for these therapies, the most effective combinations, and searching for consistent predictive factors to help select the appropriate population of LBCL patients.
At present, supporting clinical research for CAR-T ineligible patients, a new and challenging group, must remain a major focus that is complementary to advances in CAR T-cell therapy.

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