Theoretic criteria for antibody penetration into solid tumors and micrometastases.
Targeting tumors with antibody-based therapeutics is a complex task presenting multiple kinetic barriers. Antibody internalization and clearance inhibit uptake both in solid tumors, limited by tumor vascular permeability, and in micrometastases, limited by diffusion.


METHODS
A modeling exercise is used to introduce 2 simple criteria that must be less than unity for saturation of both tumors and micrometastases. The clearance modulus and the Thiele modulus are ratios of the plasma clearance rate and antibody catabolism, respectively, to the tumor tissue penetration rate.


RESULTS
Even low rates of antigen internalization from constitutive membrane turnover can significantly retard antibody penetration. Rapid clearance of single-chain variable fragments also hinders uptake, often more than counterbalancing their more rapid extravasation and diffusion.


CONCLUSIONS
The model illustrates that with the large resistance from the tumor capillary, antibodies may be more suitable for targeting micrometastases than vascularized tumors.
Thurber
Greg M
GM
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Zajic
Stefan C
SC
Wittrup
K Dane
KD
D000906:Antibodies / Q000378:metabolism*; D008954:Models, Biological; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism*
D000906:Antibodies