Targeting gastrin-releasing peptide receptors on small cell lung cancer cells with a bispecific molecule that activates polyclonal T lymphocytes.

Purpose: Gastrin-releasing peptide (GRP) is a growth factor for small cell lung cancer (SCLC). GRP belongs to the bombesin peptide family and has significant homology to bombesin. We constructed a bispecific molecule, OKT3xAntag2, by conjugating a monoclonal antibody OKT3 (anti-CD3) with a bombesin/GRP antagonist (Antag2) and evaluated cytotoxicity against SCLC cells.

Targeting gastrin-releasing peptide receptors for cancer treatment.

Growth factor receptors play critical roles in cancer cell proliferation and progression. A number of such receptors have been targeted for cancer treatment by either a monoclonal antibody or a specifically designed small molecule to inhibit the receptor function. Bombesin/gastrin-releasing peptide receptors (BN/GRP-Rs) are expressed in a variety of cancer cells and have limited distribution in normal human tissue.

Bombesin/gastrin-releasing peptide receptor: a potential target for antibody-mediated therapy of small cell lung cancer.

Purpose: Bombesin/gastrin releasing peptide (BN/GRP) is a growth factor for small cell lung cancer (SCLC). The receptor (R) for BN/GRP is overexpressed on SCLC cells and other solid tumors. BN/GRP and its receptor form an autocrine loop to promote tumor growth.

Efficient intracellular delivery of oligonucleotides formulated in folate receptor-targeted lipid vesicles.

In this study, a novel lipid vector has been developed for targeted delivery of oligodeoxynucleotides (ODN) to tumors that overexpress folate receptor. This is based on a method developed by Semple et al. (1), which utilizes an ionizable aminolipid (1,2-dioleoyl-3-(dimethylammonio)propane, DODAP) and an ethanol-containing buffer system for encapsulating large quantities of polyanionic ODN in lipid vesicles.

Caution in the use of 2-iminothiolane (Traut's reagent) as a cross-linking agent for peptides. The formation of N-peptidyl-2-iminothiolanes with bombesin (BN) antagonist (D-Trp(6),Leu(13)-psi[CH(2)NH]-Phe(14))BN(6-14) and D-Trp-Gln-Trp-NH(2).

During a study aimed at generating a bispecific molecule between BN antagonist (D-Trp(6),Leu(13)-psi[CH(2)NH]-Phe(14))BN(6-14) (Antag1) and mAb22 (anti-FcgammaRI), we attempted to cross-link the two molecules by introducing a thiol group into Antag1 via 2-iminothiolane (2-IT, Traut's reagent). We found that reaction of Antag1 with 2-IT, when observed using HPLC, affords two products, but that the later eluting peptide is rapidly transformed into the earlier eluting peptide. To understand what was occurring we synthesized a model peptide, D-Trp-Gln-Trp-NH(2) (TP1), the N-terminal tripeptide of Antag1.