Disclosed is a method of making a proteinase-engineered cancer vaccine or cancer-cell-derived spheres for treating a cancer patient, especially for cancer patients at advanced/metastatic stage. The cancer vaccine comprises dead cancer-cell-derived spheres with unbroken plasma membrane wherein the extracellular proteins and extracellular portion of membrane proteins are cleaved by proteinase digestion. The cancer vaccine may be derived from cancer cell lines or patients' cancer cells or derivatives. Also disclosed is a method of treating a cancer patient by administrating an effective amount of the cancer vaccine or cancer-cell-derived spheres to the patient. The present invention further provides a method of treating multiple diseases in addition to cancers by the cancer-cell-derived spheres, and obtaining cancer-specific immune components from blood of individuals treated with the cancer-cell-derived spheres.