cancer-research

Komatsu N, Mitsui K, Kusano-Arai O, Iwanari H, Hoshi K, Takato T, Abe T, Hamakubo T (2017) Enhancement of anti-Robo1 immunotoxin cytotoxicity to head and neck squamous cell carcinoma via photochemical internalization. Arch Can Res 5:157-163. doi: 10.21767/2254-6081.100157

Objective: To screen a monoclonal antibody to Robo1, an axon guidance receptor, for its suitability to target various cancers.

Summary: Conventional treatment exhibited an inadequate cytotoxic effect. With the addition of a photosensitizer and LED light illumination, the cytotoxic effect was remarkably improved.

Usage: Saporin-conjugated anti-Robo1 and Saporin-conjugated negative control antibody were prepared by incubating 2 mcl of 1.1 micromolar Streptavidin-ZAP (Biotin Z Internalization Kit) and 2 mcl of 1.1 micromolar biotinylated antibody for 30 min at room temperature.

Related Products: Streptavidin-ZAP (Cat. #IT-27)

Lamb YN (2017) Inotuzumab ozogamicin: First global approval. Drugs 77(14):1603-1610. doi: 10.1007/s40265-017-0802-5 PMID: 28819740

Summary: Inotuzumab ozogamicin, an anti-CD22 monoclonal antibody-calicheamicin conjugate, has received its first global approval as a promising treatment option. This novel therapy shows potential for addressing certain hematological malignancies and represents a significant advancement in the field of cancer treatment.

Lowe D, Bivens C, Mobley A, Herrera C, McCormick A, Wichner T, Sabnani M, Wood L, Weidanz J (2017) TCR-like antibody drug conjugates mediate killing of tumor cells with low peptide/HLA targets. MAbs 9:603-614. doi: 10.1080/19420862.2017.1302630

Objective: To analyze the killing potential of TCR-like ADCs.

Summary: Data comprise proof-of-principle results that TCR-like ADCs mediate potent tumor cytotoxicity and support their continued development alongside agents that disrupt DNA replication.  Additionally, TCR-like antibody ligand binding appears to play an important role in ADC functionality and should be addressed during therapy development to avoid binding patterns that negate ADC killing efficacy.

Usage: TCR-like antibodies were indirectly bound to Saporin using Mab-ZAP.  Tumor cells (5×103) were plated in flat-bottom 96-well plates, then Mab-ZAP (100 ng) was added. Various dilutions of isotype control, BB7.2, TCR-like, and 4D5 antibodies were subsequently added to a final volume of 120 mcl and plates were incubated for 3– 5 d at 37 °C with 5% CO2.

Related Products: Mab-ZAP (Cat. #IT-04)

Havelin J, Imbert I, Sukhtankar D, Remeniuk B, Pelletier I, Gentry J, Okun A, Tiutan T, Porreca F, King T (2017) Mediation of movement-induced breakthrough cancer pain by IB4-binding nociceptors in rats. J Neurosci 37:5111-5122.. doi: 10.1523/JNEUROSCI.1212-16.2017

Objective: To define a novel preclinical measure of movement-induced breakthrough pain (BTP) that is observed in the presence of morphine controlling ongoing pain.

Summary: Novel compounds targeting IB4-binding nociceptors may improve pain management for cancer pain patients and other patient populations suffering from BTP that is inadequately treated by currently available medications.

Usage: To determine the effect of eliminating input from IB4-binding fibers, separate groups of rats received spinal administration of IB4-SAP or the control, Blank-SAP (3.2 mcg/20 mcl saline) followed by a 10 mcl flush of saline. Movement of an air bubble placed between drug solution and saline was used to monitor progress of the injection.

Related Products: IB4-SAP (Cat. #IT-10), Blank-SAP (Cat. #IT-21)

Burma NE, Bonin RP, Leduc-Pessah H, Baimel C, Cairncross ZF, Mousseau M, Shankara JV, Stemkowski PL, Baimoukhametova D, Bains JS, Antle MC, Zamponi GW, Cahill CM, Borgland SL, De Koninck Y, Trang T (2017) Blocking microglial pannexin-1 channels alleviates morphine withdrawal in rodents. Nat Med 23:355-360.. doi: 10.1038/nm.4281

Summary: The authors investigated the mechanisms underlying opiate withdrawal in rat. Depletion of spinal lumbar microglia by intrathecal injections of Mac-1–SAP (Cat. #IT-33; 20 mcg) decreased withdrawal behaviors and attenuated the severity of withdrawal without affecting morphine antinociception. Unconjugated Saporin (Cat. #PR-01; 20 mcg) was used as control and had no effect on spinal CD11b immunoreactivity or naloxone-induced morphine withdrawal.

Related Products: Mac-1-SAP rat (Cat. #IT-33), Saporin (Cat. #PR-01)

Ha K, Bidlingmaier S, Su Y, Lee N, Liu B (2017) Identification of novel macropinocytosing human antibodies by phage display and high-content analysis. Methods Enzymol 585:91-110. doi: 10.1016/bs.mie.2016.10.004

Objective: To describe a method for identifying antibodies that internalize via macropinocytosis by screening phage-displayed single-chain antibody selection outputs with an automated fluorescent microscopy-based high-content analysis platform.

Summary: Novel phage antibodies are identified by colocalization with macropinocytosis marker, converted into full-length human antibodies, and further characterized with regard to cell binding, pathway of internalization, and intracellular payload delivery.

Usage: Biotinylated IgG is mixed with Streptavidin-ZAP in 1:1 molar ratio to form an immunotoxin that is serially-diluted in a cytotoxicity assay.

Related Products: Streptavidin-ZAP (Cat. #IT-27)

Nohara S, Kato K, Fujiwara D, Sakuragi N, Yanagihara K, Iwanuma Y, Kajiyama Y (2016) Aminopeptidase N (APN/CD13) as a target molecule for scirrhous gastric cancer. Clin Res Hepatol Gastroenterol 40:494-503. doi: 10.1016/j.clinre.2015.11.003

Summary: Scirrhous gastric cancer has the worst prognosis of gastric carcinoma, and treatment with standard cancer therapies has had minimal success. In this work the authors target CD13 as a marker for scirrhous gastric cancer. A gastric cancer cell line was challenged with a CD13 antibody coupled to Mab-ZAP (Cat. #IT-04) in an in vitro cytotoxicity assay. The anti-CD13 complex was more cytotoxic than an anti-EpCAM-immmunotoxin. These data, combined with flow cytometry analysis and enzyme activity assays, demonstrate the expression of CD13 as a marker for scirrhous gastric cancer.

Related Products: Mab-ZAP (Cat. #IT-04)

Hay C, Sult E, Huang Q, Mulgrew K, Fuhrmann S, McGlinchey K, Hammond S, Rothstein R, Rios-Doria J, Poon E, Holoweckyj N, Durham N, Leow C, Diedrich G, Damschroder M, Herbst R, Hollingsworth R, Sachsenmeier K (2016) Targeting CD73 in the tumor microenvironment with MEDI9447. Oncoimmunology 5:e1208875. doi: 10.1080/2162402X.2016.1208875

Summary: MEDI9447 is a human monoclonal antibody that is specific for the ectoenzyme CD73 and currently undergoing Phase I clinical trials. Here the authors show that MEDI9447 is a potent inhibitor of CD73 ectonucleotidase activity, with wide ranging immune regulatory consequences. MEDI9447 results in relief from adenosine monophosphate (AMP)-mediated lymphocyte suppression in vitro and inhibition of mouse syngeneic tumor growth in vivo. In contrast with other cancer immunotherapy agents such as checkpoint inhibitors or T-cell agonists, MEDI9447 drives changes in both myeloid and lymphoid infiltrating leukocyte populations within the tumor microenvironment of mouse models. In vitro experiments validating the internalization of antibodies into cell lines MDA-MB-231 and 4T1 were measured using the Fab-ZAP human antibody internalization kit (Cat. #KIT-51-Z). Combination data showing additive activity between MEDI9447 and anti-PD-1 antibodies using human cells in vitro and mouse tumor models further demonstrate the potential value of relieving adenosine-mediated immunosuppression. Based on these data, a Phase I study to test the safety, tolerability, and clinical activity of MEDI9447 in cancer patients was initiated (NCT02503774).

Related Products: Fab-ZAP human (Cat. #IT-51)

Palchaudhuri R, Saez B, Hoggatt J, Schajnovitz A, Sykes D, Tate T, Czechowicz A, Kfoury Y, Ruchika F, Rossi D, Verdine G, Mansour M, Scadden D (2016) Non-genotoxic conditioning for hematopoietic stem cell transplantation using a hematopoietic-cell-specific internalizing immunotoxin. Nat Biotechnol 34:738-745. doi: 10.1038/nbt.3584

Summary: To demonstrate correction of a clinically relevant disease, we employed CD45-SAP in a mouse model of sickle cell anemia and demonstrated our method achieved >90% donor cell chimerism, all mice in three groups (18/18), resulting in complete disease correction (red blood cell counts, hemoglobin levels, hematocrit levels and reticulocyte frequencies were returned to normal). If these pre-clinical results can be successfully translated to the clinic, it would greatly reduce conditioning-related toxicities and expand the use of hematopoietic stem cell transplantation.

Related Products: Streptavidin-ZAP (Cat. #IT-27), Anti-CD45.2-SAP (Cat. #IT-91)

Read the featured article in Targeting Trends.

Palchaudhuri R (2016) Featured Article: Targeted depletion of hematopoietic stem cells promises safer transplantation. Targeting Trends 17(3)

Related Products: Streptavidin-ZAP (Cat. #IT-27)

Read the featured article in Targeting Trends.

See Also:

• Palchaudhuri R et al. Non-genotoxic conditioning for hematopoietic stem cell transplantation using a hematopoietic-cell-specific internalizing immunotoxin. Nat Biotechnol 34:738-745, 2016.
• Skulimowska I et al. The biology of hematopoietic stem cells and its clinical implications. FEBS J 16192, 2021.