Immunotherapy compositions and methods

1. A binding molecule comprising:

a binding domain having specificity for a tumor antigen, and

a recognition domain, wherein the recognition domain comprises a small molecule less than about 5 kilodaltons in size,

wherein the binding domain is covalently linked to the recognition domain, and wherein the binding domain is an antibody, an affimer, or a T-cell receptor (TCR) multimer,

wherein the recognition domain is linked to a protection domain such that the recognition domain is masked,

and wherein the protection domain comprises a protease susceptible peptide.

2. The binding molecule of claim 1 , wherein the recognition domain specifically binds to a secondary binding molecule, and wherein the secondary binding molecule is on a cell, and wherein the cell is a chimeric antigen receptor T-cell (CAR T), a T-lymphocyte, a B-lymphocyte or natural Killer cell.

3. The binding molecule of claim 2 , wherein the antibody is a Fab or a scFV; or wherein the TCR multimer is a tetramer.

4. The binding molecule of claim 1 , wherein the protection domain comprises a carrier domain linked to a protease susceptible peptide; or

wherein the protection domain comprises a masking peptide and a masking polymer; or

wherein the protection domain is pH sensitive.

5. The protection domain of claim 4 , wherein the masking polymer is PEG-diacrylate; or

wherein the masking peptide comprises the amino acid sequence LysSerGlyProLeuGlyValArgGlySerSerCys (SED ID NO: 18); or

wherein the masking peptide comprises a cleavable peptide.

6. The binding molecule of claim 4 , wherein when the protection domain is contacted with a protease, the recognition domain is unmasked; and wherein when the protection domain is at a specific pH, the recognition domain is unmasked.

7. The binding molecule of claim 4 , wherein the carrier domain is a polypeptide or a polymer; wherein the polymer is PEG-diacrylate.

8. The binding molecule of claim 6 , wherein the protease susceptible peptide is specific for a tumor protease.

9. The binding molecule of claim 1 , wherein the small molecule is:

(a) synthetic or naturally-occurring;

(b) biologically active or inactive;

(c) a drug, a toxin, a hormone, a metal, a cytokine, a peptide or a nucleic acid;

(d) fluorescein isothiocyanate (FITC), anthraquinone-2-acid, an amphetamine, a benzodiazepine, a benzoylecgonine, a buprenorphine, an opioid, a cannabinoid, a phencyclidine or a tricyclic antidepressant; or

(e) dextromethorphan, fentanyl, meprobamate, methadone, methamphetamine, oxycodone, THC, tramadol, Zolpidem, ketamine, LSD, MDMA, methaqualone, propoxyphene or norketimine.

10. The binding molecule of claim 9 , wherein the recognition domain comprises fluorescein isothiocyanate (FITC) or anthraquinone-2-acid.

11. The binding molecule of claim 1 , wherein the binding domain is an antibody.

12. The binding molecule of claim 2 , wherein the cell is a chimeric antigen receptor T-cell (CAR-T).