Photoimmunotherapy has been established as a potential and highly selective cancer therapy against EGFR, HER2, PSMA, and CD25 postive tumors. All targeted cells are killed by necrotic cell death after irreversible damage to the cell membrane immediately after exposure to near infrared light at 690 nm. We are currently investigating precise mechanisms of membrane damage. We are also expanding the repertoire of potential target molecules to include MUC1, CEA, laminine, GPC3, mesothelin, etc. by obtaining new antibodies for covering wider varieties of cancer. Additionally, we are also establishing novel non-invasive imaging methods to diagnose the therapeutic effects of PIT because necrotic cell killing induced by PIT is a very rapid process and cells die well in advance of changes of physical appearance on conventional images. We have recently discovered that PIT dramatically increases (20-fold) the delivery of nanoparticle sized therapies (e.g. liposomal chemotherapy) to PIT-treated cancer tissue. Therefore, the combination of PIT with nano-sized cancer reagents holds potential for even more effective therapy. Finally, we are now preparing clinical trials in head and neck and esophageal squamous cell cancer at NCI/Hopkins, National Cancer Center Singapore, and Netherland/Groningen Univ in collaboration with surgeons at these sites. We are working with the Image Probe Development Center (IPDC) to scale up production of antibody-IR700 conjugates for eventual use in these trials.