Methods for generating and identifying antibodies specifically binding target molecules expressed by cells embedded in a three-dimensional extracellular matrix resembling the in vivo environment and form of the target are provided. Also provided are methods of producing immunogens that yield targets in such forms. Further provided are methods for identifying anti-cancer therapeutics, such as antibody products. Hydrogels are also provided, and those hydrogels may comprise a cross-linked protein are also provided. Diagnostics, prophylactics and therapeutics identified using the methods disclosed herein are also provided.
