Provided herein are anti-TREM2 antibodies and related methods of making and using anti-TREM2 antibodies. Also provided are methods and compositions for enhancing an immune response and/or for the treatment of an immune-related condition in an individual, e.g., cancer, comprising killing, disabling, or depleting non-stimulatory myeloid cells using an anti-TREM2 antibody or antigen binding fragment thereof.

A nanoagent for detections and treatments of multiple targets of interest includes multiple types of nanocomposites, each type of nanocomposites comprising at least one nanostructure, each nanostructure having a core and a shell surrounding the core; a respective reporter assembled on the shell of each nanostructure; and a layer of a respective treating agent and a respective targeting agent conjugated to the respective reporter. In use, each type of nanocomposite targets to a respective target of interest according to the respective targeting agent and releases the respective treating agent and the nanostructure therein for therapeutic treatment of the respective target of interest, and the respective target of interest transmits at least one signature responsive to the respective reporter for detection of the respective target of interest.

The present invention relates to methods for preparing an animal tissue for fluorescence microscopy, to an animal tissue obtainable by said methods, to methods for analyzing said animal tissues, and to methods for the detection of metastases, for analyzing the biodistribution of a biopharmaceutical drug, and for analyzing the biodistribution of nanoparticles. The methods for preparing an animal tissue according to the present invention encompass whole-body labeling, clearing and imaging methods. The methods of the invention are advantageous in that they, for instance, allow the visualization of single cells within mammalian tissues including pig and human brains, tumor metastases at the single cell level and of the distribution of biopharmaceutical drugs (e.g. the distribution of cancer-targeting therapeutic antibodies in whole animals such as intact mice) at single cell level in whole mouse.

Methods of predicting response of a subject suffering from cancer to an anti-PD-1/L1 immunotherapy, as a monotherapy or combination therapy, comprising calculating a resistance score for factors expressed by the subject, summing the resistance score to produce a total resistance score, wherein a total resistance score beyond a predetermined threshold indicates a subject is predicted to be resistant to the anti-PD-1/L1 immunotherapy as a monotherapy or combination therapy, are provided.

Provided is an adapter comprising an antibody binding domain (AbBD) that specifically binds and crosslinks to an immunoglobulin Fab region, where the AbBD is a variant of a Protein A domain D and has an amino acid replacement/modification at A28, G32, Q35, S36, N46, G49, E50, K53 or L54 of SEQ ID NO: 1 or combinations thereof, and where the AbBD is photoreactive. Also provided is an adapter comprising an AbBD that specifically binds and crosslinks to an IgG Fab region and/or to an immunoglobulin M (IgM) Fab region, where the AbBD is a variant of a Protein A domain D and has an amino acid replacement/modification at A28, E50, or L54 of SEQ ID NO: 1 or combinations thereof, where the AbBD is photoreactive. Provided is an adapter comprising an AbBD that specifically binds and crosslinks to an IgG Fab region, where the AbBD is a variant of a Protein L C* domain and has an amino acid replacement/modification at G22 or T46 of SEQ ID NO: 2 or a combination thereof, wherein the AbBD is photo-reactive. Methods for using the AbBD for imaging, diagnosing and/or treating a disease are provided.

A construction method for constructing a benign-malignant pulmonary nodule differential diagnosis model based on a single-cell immune atlas provided. In this method, PBMCs are obtained by utilizing peripheral blood samples, followed by CyTOF analysis to generate a CyTOF dataset. Using Phenotype Analysis and Representation Clustering (PARC) algorithm, cells are categorized into distinct phenotypes based on marker expression, and the frequencies of cell subsets are employed as potential modeling features that are finally selected by using the RF method with 10-fold cross-validation strategy, thereby enabling lung cancer screening and early diagnosis. This technology is characterized by its non-invasiveness, high sensitivity, and high specificity, improving the diagnostic accuracy of lung cancer screening and providing patients with earlier treatment opportunities and more suitable surgical approaches.

Antibodies that bind to AXL protein and variants thereof are described herein. AXL exhibits a distinct and limited expression pattern in normal adult tissue(s), and is aberrantly expressed in the cancers listed in Table I. Consequently, the MAbs of the invention provide a diagnostic composition for the treatment and management of cancer.

The present disclosure provides monoclonal antibodies that recognize human Nectin-2 (Nectin-2, Poliovirus Receptor-Related Protein-2, Poliovirus Receptor-Like 2, CDI12, or PRR-2, is a single pass transmembrane glycoprotein with two Ig-like C2-type domains and an Ig-like V-type domain) with high affinity and specificity and inhibit its binding to TIGIT and/or CD112R. The antibodies recognize the Nectin-2 protein (CD112), prevent its binding to T cell immunoreceptor with Ig and ITIM domains (TIGIT) and CD112R (PVRIG) and inhibit suppressive activity on lymphocytes such as natural killer (NK) cells and T-cells. The disclosure further provides pharmaceutical and methods for use in cancer immunotherapy and in diagnosis. The disclosure finally further provides chimeric antigen receptor (CAR) comprising scFv antibody binding to Nectin-2.

Provided herein are biomarkers for the treatment of pathological conditions, such as cancer, and method of using PD-1/PD-L1 pathway antagonists. In particular, provided are biomarkers for patient selection and prognosis in cancer, as well as methods of therapeutic treatment, articles of manufacture and methods for making them, diagnostic kits, methods of detection and methods of advertising related thereto.

The present invention is directed to anti-PVRIG antibodies and stable liquid pharmaceutical formulations thereof. The present invention is directed to monotherapy and combination treatments with anti-PVRIG antibodies and anti-PD-1 antibodies, in particular nivolumab, using stable liquid pharmaceutical formulations thereof. The present invention also provides biomarkers for use in determining populations for treatment with anti-PVRIG antibodies and such biomarkers include, for example PVRIG and/or PVRL2 expression.