The present invention relates to an in vitro method for the prognosis of disease progression in a patient that suffers from or is at risk of developing cancer, said method comprising the step of determining, in a sample from said patient which is suspected to comprise neoplastic or cancerous tissue, whether or not the sample comprises a tertiary lymphoid structure (TLS), and prognosing disease progression, wherein the prognosis is an assessment regarding the likelihood of improved survival of the patient, and/or better clinical outcome of an immunotherapy.

Methods of assessing a graft recipient's predisposition to reject a transplant are provided. The risk of transplant rejection may be assessed in a subject prior to transplant, wherein subjects having a greater immune repertoire diversity prior to transplant are more susceptible to transplant rejection. Also, increases in immune repertoire diversity after transplant are indicative of transplant risk after. In another aspect, the presence or elevated abundance of immune elements comprising IGHV3-23 sequences are indicators of transplant rejection risk. In another aspect the scope of the invention encompasses methods of treating transplant rejection in a subject, by assessing transplant risk and administering immunosuppressive therapy in accordance with assessed risk.

Biological activity in holding pens in a micro-fluidic device can be assayed by placing in the holding pens capture objects that bind a particular material of interest produced by the biological activity. The biological material of interest that binds to each capture object can then be assessed, either in the micro-fluidic device or after exporting the capture object from the micro-fluidic device. The assessment can be utilized to characterize the biological activity in each holding pen. The biological activity can be production of the biological material of interest. Thus, the biological activity can correspond to or arise from one or more biological cells. Biological cells within a holding pen can be clonal cell colonies. The biological activity of each clonal cell colony can be assayed while maintaining the clonal status of each colony.

The present invention provides a method for determining whether a Rheumatoid Arthritis (RA) patient is susceptible to treatment with a B cell targeted therapy, which method comprises the step of analysing B cells and/or germinal centre-like structures (GC-LS) in a synovial tissue sample from the patient; wherein a patient whose synovial tissue sample is B cell rich and/or GC-LS negative is determined to be susceptible to treatment with the B cell targeted therapy, whereas a patient whose synovial tissue sample is B-cell poor and/or GC-LS positive is determined to be resistant to treatment with the B cell targeted therapy.

Aspects of the disclosure relate to compositions and methods for treating certain (e.g., CD33-positive) cancers. In some aspects, the disclosure provides antibodies that specifically bind to CD33 protein variants that lack an IgV domain. In some aspects, the disclosure provides adaptable cell engagers (ACEs) and recombinant proteins (e.g., BiTEs) comprising an anti-CD33 antibody of the disclosure and an anti-CD3 antibody. In some embodiments, the disclosure provides methods of treating cancer by administering the antibodies, ACEs, or recombinant proteins (e.g., BiTEs) to a subject in need thereof.

The present invention relates to methods for efficiently generating recombinant monoclonal antibodies derived from B cells of a non-human host which has been immunochallenged with one or more target antigens. The methods comprise the steps of identifying and isolating B cell that bind to the antigen by FACS, and recombining and enriching for thousands of cells to create a B cell library. Related products and methods, such as methods of producing expression libraries, are also disclosed.

Compositions and methods for determining the efficacy and/or potency of a vaccine preparation are described herein. Splenocytes from immunized animals are isolated and frozen. Upon thawing aliquots these cells are activated by exposure to a series of dilutions of q vaccine preparation being tested and a series of dilutions of a reference vaccine with known characteristics. Cells secreting immunogen-specific antibody and cells secreting nonspecific antibody are enumerated, as is the amount of immunogen-specific and nonspecific antibody produced. Comparison between the results from the vaccine preparations provides a measure of relative vaccine efficacy and/or potency.

In one aspect, methods of generating human monoclonal antibodies that specifically binds to an allergen are provided. In some embodiments, the monoclonal antibodies are generated from sequences identified from isolated single B cells from a human subject who is allergic to the allergen.

This invention provides methods for diagnosing Alzheimer's disease in a symptomatic human subject, and for determining whether a human subject is predisposed to becoming afflicted with Alzheimer's disease. These methods employ the steps of (a) culturing a subject's lymphocytes with a suitable basement membrane matrix to permit the lymphocytes to aggregate; (b) measuring the resulting lymphocyte aggregation; and (c) based on such measurement, either diagnosing Alzheimer's disease or determining a predisposition to it, as appropriate.

In vitro biomimetic models of the neonatal immune system are provided along with methods of using the models in pre-clinical assessment of infant immune cell-mediated and humoral responses to immunogenic stimulation, such as vaccination. The models include one comprising cord blood-derived T follicular helper cells and B cells, and one comprising cord blood-derived dendritic cells and CD4+ T cells. The models can be used, for example, to assess candidate vaccines via analysis of cellular responses to antigen and vaccine exposure.