Nucleic acid molecules that include a nucleotide sequence encoding a chimeric antigen receptor (CAR) and a nucleotide sequence encoding a protease sensitive scFv, wherein the chimeric antigen receptor comprises: an scFv targeting a tumor antigen, a spacer, a transmembrane domain, a co-stimulatory domain, and a CD3 ? signaling domain; and the protease-sensitive scFv and the scFv target the same tumor antigen are described.

Embodiments relate to a modified cell comprising a polynucleotide encoding an antigen binding molecule and a polynucleotide encoding an agent targeting one or more extracellular matrix (ECM) molecules. In embodiments, the polynucleotide encoding the agent comprises at least a nucleic acid encoding Cathepsin K (CK), a nucleic acid encoding Neutrophil Elastase (NE), or a nucleic acid encoding MMP7. In embodiments, the nucleic acid encoding NE comprises a nucleic acid encoding NE and a nucleic acid encoding a signaling domain of IL2. In embodiments, expression of the polynucleotide encoding the agent is regulated by hypoxia-inducible factor 1-alpha (HIF1?), nuclear factor of activated T-cells (NFAT), forkhead box P3 (FOXP3), or nuclear factor kappa B (NF-?B).