Bispecific antibodies redirect synthetic agonistic receptor modified T cells against melanoma.

Background: Melanoma is an immune sensitive disease, as demonstrated by the activity of immune check point blockade (ICB), but many patients will either not respond or relapse. More recently, tumor infiltrating lymphocyte (TIL) therapy has shown promising efficacy in melanoma treatment after ICB failure, indicating the potential of cellular therapies. However, TIL treatment comes with manufacturing limitations, product heterogeneity, as well as toxicity problems, due to the transfer of a large number of phenotypically diverse T cells.

T cell-derived interleukin-22 drives the expression of CD155 by cancer cells to suppress NK cell function and promote metastasis.

Although T cells can exert potent anti-tumor immunity, a subset of T helper (Th) cells producing interleukin-22 (IL-22) in breast and lung tumors is linked to dismal patient outcome. Here, we examined the mechanisms whereby these T cells contribute to disease. In murine models of lung and breast cancer, constitutional and T cell-specific deletion of Il22 reduced metastases without affecting primary tumor growth.

Long non-coding RNAs in cancer stem cells.

In recent years, it has been evidenced that the human transcriptome includes several types of non-coding RNAs (ncRNAs) that are mainly involved in the regulation of different cellular processes. Among ncRNAs, long-non-coding RNAs (lncRNAs) are defined as longer than 200 nucleotides and have been shown to be involved in several physiological and pathological events, including immune system regulation and cancer. Cancer stem cells (CSCs) are defined as a population of cancer cells that possess characteristics, such as resistance to standard treatments, cancer initiation, ability to undergo epithelial-to-mesenchymal transition, and the ability to invade, spread, and generate metastases.

Chimeric Antigen Receptor-Modified T Cells and T Cell-Engaging Bispecific Antibodies: Different Tools for the Same Job.

Purpose Of Review: Both chimeric antigen receptor (CAR) T cells and T cell-engaging antibodies (BiAb) have been approved for the treatment of hematological malignancies. However, despite targeting the same antigen, they represent very different classes of therapeutics, each with its distinct advantages and drawbacks. In this review, we compare BiAb and CAR T cells with regard to their mechanism of action, manufacturing, and clinical application.

A modular and controllable T cell therapy platform for acute myeloid leukemia.

Targeted T cell therapy is highly effective in disease settings where tumor antigens are uniformly expressed on malignant cells and where off-tumor on-target-associated toxicity is manageable. Although acute myeloid leukemia (AML) has in principle been shown to be a T cell-sensitive disease by the graft-versus-leukemia activity of allogeneic stem cell transplantation, T cell therapy has so far failed in this setting. This is largely due to the lack of target structures both sufficiently selective and uniformly expressed on AML, causing unacceptable myeloid cell toxicity.

β-AR blockade potentiates MEK1/2 inhibitor effect on HNSCC by regulating the Nrf2-mediated defense mechanism.

The β2-Adrenergic receptor (β2-AR) is a G protein-coupled receptor (GPCR), involved in the development of many cancers, among which HNSCC. In this contest, β2-AR signaling interacts with different pathways, such as PI3K and MAPK, commonly activated by TK receptors. For this reason, TK blockade is one of the most adopted therapeutic strategies in HNSCC patients.

The role of autophagy in resistance to targeted therapies.

Autophagy is a self-degradative cellular process, involved in stress response such as starvation, hypoxia, and oxidative stress. This mechanism balances macro-molecule recycling to regulate cell homeostasis. In cancer, autophagy play a role in the development and progression, while several studies describe it as one of the key processes in drug resistance.

Virus-like vaccines against HIV/SIV synergize with a subdominant antigen T cell vaccine.

Background: In non-human primates (NHPs) and humans, partial protection from HIV/SIV infection or suppression of replication is achievable by Env-binding antibodies and Gag-specific CD8+ T-cells targeting protective epitopes. Unfortunately, such T-cell responses are frequently dominated by responses to non-protective, variable epitopes. In this study we attempt to combine three independent approaches, each developed to prevent immunodominance of non-protective epitopes.

Virus-Like-Vaccines against HIV.

Protection against chronic infections has necessitated the development of ever-more potent vaccination tools. HIV seems to be the most challenging foe, with a remarkable, poorly immunogenic and fragile surface glycoprotein and the ability to overpower the cell immune system. Virus-like-particle (VLP) vaccines have emerged as potent inducers of antibody and helper T cell responses, while replication-deficient viral vectors have yielded potent cytotoxic T cell responses.