772 Novel RNA-nanoparticle vaccine for the treatment of early melanoma recurrence following adjuvant anti-PD-1 antibody therapy

Background Melanoma is an increasing public health concern. Immune checkpoint inhibitors (ICI) has revolutionized the treatment of advanced melanoma. Unfortunately, in the adjuvant setting, up to 30% of subjects have disease recurrence within 1 year of treatment. Previous studies have shown that subjects who progress while on adjuvant ICI, or soon after completion, have a… Continue reading 772 Novel RNA-nanoparticle vaccine for the treatment of early melanoma recurrence following adjuvant anti-PD-1 antibody therapy

605 Computational pathology-based digital twins enable the discovery of predictive biomarkers for precision immuno-oncology

AI SummaryDigital Twins based on imaging data can be used to generate virtual randomized and biomarker stratified Phase III clinical trials. This approach was demonstrated using data from single-arm Phase I/II trials and historical Standard-of-Care data. The study shows the technical feasibility of this methodology and suggests that it could improve the success rate of… Continue reading 605 Computational pathology-based digital twins enable the discovery of predictive biomarkers for precision immuno-oncology

594 SQZ-PBMC-HPV-101: Increased overall survival in a subset of patients with recurrent, locally advanced, or metastatic HPV16+ tumors treated with cell-based vaccine, SQZ-PBMC-HPV

AI SummaryA cancer vaccine called SQZ-PBMC-HPV, which delivers antigens directly into cells, showed promising results in patients with advanced HPV16 cancers. The vaccine increased the density of CD8+ T cells in tumors, resulting in longer overall survival and better control of tumor growth compared to patients without increased CD8 density. The treatment was generally well-tolerated… Continue reading 594 SQZ-PBMC-HPV-101: Increased overall survival in a subset of patients with recurrent, locally advanced, or metastatic HPV16+ tumors treated with cell-based vaccine, SQZ-PBMC-HPV

508 IL-15-stimulated NK cell proliferation is greatly augmented by the anti-ADAM17 mAb Medi-1 and requires CD137

Background Natural killer (NK) cells are innate cytolytic lymphocytes that can directly and rapidly kill malignantly transformed cells without clonal expansion. While NK cell adoptive transfer has shown clinical benefits in cancer patients, this approach requires cytokine support for the NK cells to persist, which IL-15 is commonly used. Cytokine stimulation of NK cells activates… Continue reading 508 IL-15-stimulated NK cell proliferation is greatly augmented by the anti-ADAM17 mAb Medi-1 and requires CD137

524 The association between mesothelial membranes metastasis and response to immune checkpoint inhibitors in solid tumors

Background Specific anatomic sites of metastasis (mets) such as liver and brain have been associated with poor response to immune checkpoint inhibitors (ICIs). The association between mesothelial membranes (MMs) mets and response to ICIs in solid tumors has not been established. Herein, we explored the association between MMs mets and response to ICIs. Methods A… Continue reading 524 The association between mesothelial membranes metastasis and response to immune checkpoint inhibitors in solid tumors

522 Quantitative proteomic profiling of KZR-540, a novel small molecule oral Sec61 inhibitor that selectively inhibits PD-1 expression

Background Secreted and transmembrane proteins are integral in promoting cancer cell proliferation as well as tumor growth, immune evasion, and metastasis. Most of these proteins require translocation through the Sec61 translocon complex (Sec61) for entry into the endoplasmic reticulum (ER) and progression to the cell membrane. Inhibiting programmed cell death 1 (PD-1), a Sec61 client… Continue reading 522 Quantitative proteomic profiling of KZR-540, a novel small molecule oral Sec61 inhibitor that selectively inhibits PD-1 expression

521 mRNA encoded antibodies improve biodistribution and efficacy of checkpoint inhibitors for liver cancer

AI SummaryLipid nanoparticle (LNP) encapsulated mRNA is a promising method for delivering therapeutic proteins to specific tissues. This study focuses on liver tropic delivery of a novel mRNA encoded bispecific antibody for hepatocellular carcinoma (HCC). The results show that this method has favorable pharmacokinetics and biodistribution, and is more effective than recombinant antibodies in treating… Continue reading 521 mRNA encoded antibodies improve biodistribution and efficacy of checkpoint inhibitors for liver cancer

503 KH-801, a differentated humanized anti-CD24 antibody, potentiates the effects of immunomodulatory and anti-tumor activity in preclinical cancer models with favorable safety profiles

Background CD24 is a small GPI-anchored, highly glycosylated membrane protein, which interacting with Siglec-10 on TAMs (Tumor Associated Macrophages) acting as ‘don’t eat me’ signals, and helping tumor cells avoid being engulfed by macrophages. CD24 is widely detected in many solid tumors.1 We have developed a unique humanized anti-CD24 antibody, KH-801, that depletes tumor cells… Continue reading 503 KH-801, a differentated humanized anti-CD24 antibody, potentiates the effects of immunomodulatory and anti-tumor activity in preclinical cancer models with favorable safety profiles

499 Myeloid diversity in hormone receptor positive breast cancer reveals myeloid and lymphoid signaling pathways that correlate with T cell inhibition

Background Targeting the body’s own immune system to fight cancer has focused on activating T cells through immune checkpoint blockade (ICB). Because ICB agents work by reinvigorating pre-existing T cells, it is less likely that these agents will be effective in tumors with low levels of T cell infiltrate. Hormone receptor positive (HR+) breast cancer… Continue reading 499 Myeloid diversity in hormone receptor positive breast cancer reveals myeloid and lymphoid signaling pathways that correlate with T cell inhibition

440 Preclinical safety assessment for specificity of biotherapeutics using the membrane proteome array

AI SummaryThe Membrane Proteome Array (MPA) platform was developed to assess the specificity of monoclonal antibodies. It has been successful in identifying lead antibody candidates that do not display cross-reactivity with other proteins. The MPA has been accepted by the FDA and may be developed as a qualified Drug Development Tool.Background Rigorous specificity analysis is… Continue reading 440 Preclinical safety assessment for specificity of biotherapeutics using the membrane proteome array