Weekly Digests

2020

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Release the B7.1! Anti-PD-L1 breaks PD-L1’s grip

April 1, 2020

Blocking the PD-1/PD-L1 axis using anti-PD-L1 antibodies is a commonly employed immunotherapeutic strategy to prevent PD-1-mediated inhibition of T cells by tumor cells. Suspecting that the mechanism of action of PD-L1 blockade might be more complex, however, Mayoux et al. investigated the role of PD-L1-expressing dendritic cells (DCs) in PD-L1 blockade. The results...

Special announcement

March 25, 2020

To All Our Readers, The COVID-19 crisis has dominated the world's attention and caused major changes in all our lives. To give our team members the chance to adjust to this ever-intensifying landscape we decided to take a brief 2 week pause in publishing our newsletter. Despite this pause, our staff and our volunteers...

Bee venom throws a one-two punch to kill the tumor

March 18, 2020

Targeting the tumor where it lives and turning the tumor against itself was what Yu and Dai et al. had in mind when they developed a one-two punch nanovaccine comprising a lipid nanoparticle (NP) loaded with melittin (a peptide found in European bee venom), called α-melittin-NP. The vaccine, which contained no tumor antigens...

Put me in, coach! Peripheral T cells are ready to play

March 11, 2020

In an effort to investigate the origin, behavior, and fate of T cells in patients with cancer, Wu et al. sequenced 330 million mRNA transcripts from 141,623 T cells, which had been isolated from the tumors and normal adjacent tissue (NAT) of 14 treatment-naive patients with 4 different types of cancer; peripheral blood...

Zeroing in on intratumoral Tregs via CD36

March 4, 2020

With the goal of selectively disrupting intratumoral Tregs without inducing systemic autoimmunity, Wang et al. hypothesized that intratumoral Tregs must metabolically adapt to the harsh conditions of the tumor microenvironment (TME), and therefore explored metabolic pathways that could potentially target Tregs exclusively within the TME to find actionable targets. The results, recently published...

T cells CRISPRed to perfection for attack on refractory cancer

February 26, 2020

Aiming to improve the safety and efficacy of engineered T cells for the treatment of human cancers, Stadtmauer and Fraietta et al. utilized CRISPR-Cas9 genome editing to knock out PD-1 (PDCD1) and the endogenous TCR α and β chains (TRAC and TRBC) in autologous T cells that also expressed an exogenous TCR targeting...

CAR NK cells – the newest drivers on the road

February 19, 2020

The powerful effects of CD19-targeting CAR T cells against blood cancers have been well documented in a high portion of treated patients. However, CAR T cells can induce significant toxicities, and the fact that this treatment must be personalized makes the manufacturing process slow, challenging, and expensive. In early results from a phase...

Bispecific antibody 7370: will AML meet its match?

February 12, 2020

In an effort to address the significant unmet clinical needs in the treatment of acute myeloid leukemia (AML), Yeung and Krishnamoorthy et al. developed a novel bispecific antibody that targets both CD3 on T cells and FLT3 on AML cells. FLT3 was selected as a strong potential target antigen, given its upregulated expression...

The holy grail: pan-cancer-targeting T cells

February 5, 2020

The holy grail of cancer research is finding one treatment that kills all types of cancer in every affected individual. With this lofty goal in mind, Crowther and Dolton et al. explored unconventional T cells and identified a T cell clone capable of killing many different types of cancer in an HLA-independent fashion...

Special delivery! An oncolytic virus encoding IL-7 and IL-12

January 29, 2020

The immune status of the tumor microenvironment (TME) is known to be a key factor influencing the success or failure of cancer immunotherapy. In an effort to improve the immune status of the TME, Nakao et al. tested the intratumoral delivery of oncolytic viruses encoding IL-7 and IL-12, and saw encouraging local and...

PD-1 in myeloid cells prevents tumor control

January 22, 2020

Aiming to uncover the role that the expression of PD-1 in various cell types plays in antitumor immunity, Strauss et al. analyzed the effects of selective PD-1 ablation in myeloid cells and T cells, and surprisingly found that knockout of PD-1 in myeloid cells, but not in T cells, was crucial for an...

Kickstarting the cancer immunity cycle with AGI-134

January 15, 2020

The cancer immunity cycle starts and ends with cancer cell death, and inducing cancer cell death at the site of a tumor to kickstart antitumor immunity is a developing strategy in cancer immunotherapy. One approach that has been explored to induce cancer cell death in situ is the introduction of α-Gal epitopes, which...

Stem-like CD8+ T cells cozy up within tumors before launching an attack

January 8, 2020

Since the infiltration of CD8+ T cells into tumors predicts survival and response to immunotherapy in many patients, Jansen et al. examined the CD8+ T cell response against human cancer in order to understand why some tumors have high CD8+ T cell infiltration while others do not, and to uncover the mechanisms behind...

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