University at Buffalo
The Witebsky Center

The Witebsky Center
University at Buffalo
Bacteriology hostmicrobe immunology parasitology virology bioinformatics mycology
The Witebsky Center The Witebsky Center
Kate Rittenhouse-Olson, Ph.D.

Kate Rittenhouse-Olson, Ph.D., S.I. CM Associate Professor 
Department of Biotechnical & Clinical Laboratory Sciences
44 Cary Hall
Phone: 829-3630


My research for the last 22 years has focused on carbohydrate antigens that are important in cancer and in infectious disease (bacterial, viruses and parasites). These structures play important roles in the growth, adhesion and spread of cancer cells and bacteria and viruses. Immune responses to these structures can therefore be an effective mechanism to decrease disease. The anti-carbohydrate immune response is usually T cell independent, more difficult to develop and less in magnitude than the immune response to proteins. My long-term goals involve using information obtained about carbohydrates of related structures to manipulate the anti-carbohydrate immune response to improve clinical outcome.  This work has involved use of synthetic oligosaccharides conjugated to bovine serum albumin as antigens, the use of structurally related synthetic oligosaccharides in inhibition studies, the use of antibody to carbohydrates in immunotherapy and immunolocalization of cancer, the use of genetic analysis of genes related to carbohydrate synthesis and adhesion, bacterial vaccine stability assays and bacteria rapid diagnosis assay development.  The immunochemical aspects of this work were performed to determine the immunodominant regions of the sugars and the effects of small structural changes in the inhibitory oligosaccharides on the immunologic reaction. 
My laboratory, RPCI based for the first 9 years, and now at UB for the last 13 years, has had an emphasis on tumor associated carbohydrate antigens, and recently has been involved in 2 patent applications, “Use of anti-TF antibody to block metastasis of TF- antigen bearing tumors” (K R Olson, principle inventor of JAA-F11 monoclonal antibody), and “Carbohydrate Antigen-Nanoparticle Conjugates and Methods for Inhibiting Metastasis in Cancer” (K R Olson, co-inventor). Thomsen-Friedenreich antigen (TF-Ag) is a tumor associated antigen that is exposed in many types of carcinoma cells including breast, prostate, colon, and bladder. My laboratory recently reported results from in vitro and in vivo studies that show the anti-metastatic effect of treatment with JAA-F11 antibody to TF- Ag on the mouse metastatic breast carcinoma 4T1 cells..  The anti-TF antibody metastasis work was just published in Neoplasia (vol 8 number 11) and is the featured article, with cover art.  A portion of this work   involved collaborative studies showing our anti-TF-Ab effect on in vitro and ex vivo models of metastasis (Dr. Glinskii, University of Minnesota).  A related, recently submitted, study utilized Micro-PET to assess the ability of this antibody to immunoradiolocalize in a mouse metastatic breast tumor model (in collaboration with Drs. Sajjad and Hani Nabi, Nuclear Medicine, UB)..  To determine the clinical utility of immunoradiolocalization with this antibody, collaborations have begun with Dr. Dick Bankert (UB) with a SCID ovarian tumor model and Dr. Betsy Repasky (RPCI).  The carbohydrate antigen-nanoparticle patent application is in collaboration with Dr. Joseph Barchi of NCI and involves the same carbohydrate tumor associated antigen, Thomsen Friedenreich antigen (TF-Ag). We feel that this TF-Ag conjugate nanoparticle, in addition to its clinical potential, may help us further understand the metastatic process.Collaborative studies with this drug are ongoing in my laboratory. 

Other studies on the TF-ag involve trying to create an immune response to this antigen in the cancer patient, since passive transfer with Ab to this marker had an anti-metastatic effect.  As stated earlier, carbohydrate antigens do not provoke the same type of immune response as protein antigens.  The response to carbohydrate antigens is T independent and may not form at all in infants under 2 years of age, in geriatric patients, and in patients receiving chemotherapy or radiation therapy.  In addition, in the case of carbohydrate tumor associated antigens the patient may be tolerant to their tumor associated carbohydrate antigen, but if presented with the antigen in a more immunogenic form, tolerance may be broken.  Peptide mimicry of carbohydrate antigens has been shown to be possible, and my laboratory has begun to develop peptide mimics for our carbohydrate antigen Gal b 1-3GalNAc through the use of a commercially available phage display library. In the procedure that was used, the peptide library is expressed on the terminus of the adsorption protein of m13 phage. We used the monoclonal antibody to the TF-Ag as a capture antibody to isolate phage which express a peptide mimic of the TF-Ag, and followed this reaction with a rabbit polyclonal Ab to TF-Ag.  In preliminary EIA analysis we found that nine of these isolated clones from phage inhibited the interaction of our antibody (Ab) with the TF- Ag. We found 3 clones which reacted to the mouse monoclonal Ab, with the rabbit ab and with peanut lectin, a lectin which binds the TF- Ag structure.   Further experiments showed that one of these mimics inhibited tumor cell adhesion to the vascular endothelium to a similar extent as the anti-TF Ab.  Immunizations with these mimics produced small amounts of anti-TF Ab and further research is being performed to increase the immunogenicity of the mimics.  The above studies are supported by a Dept of Defense predoctoral award to Jamie Heimburg, a recent PhD graduate.

Ongoing studies are attempting to further understand the anti- metastatic role of antibody to TF-Ag by using cell lines which are related to 4T1, but with different metastatic potentials. These cell lines were analyzed by Glyco-gene chip array, real-time quantitative reverse transcriptase polymerase chain reaction, and flow cytometry. The Glyco-gene chip array allows for analysis of 1800 genes related to either carbohydrate antigen production or carbohydrate binding. Differential mRNA expression and flow cytometric analysis of cell surface expression of different carbohydrate genes and adhesion molecules were investigated to determine how they relate to cancer metastasis.  These analyses confirmed that there is differential surface expression of the adhesion molecules,and surface carbohydrates between the different cell lines. Knowledge concerning the carbohydrate interactions involved in metastasis will enable future therapies targeted at blocking metastasis. This work was done in collaboration with the Consortium for Functional Glycomics, (Tim Gilmartin, Steve Head, Scripps Institute) for the Glyco-gene chip analysis and will continue with glycan analysis with (Anne Dell, Stuart Haslam, Simon North, Division of Molecular Biosciences, Imperial College, London).

Recent publications

 Li, G.,  Pandey, S.K. Pandey, Dobhal,M.P., Mehat, R., Chen, Y., Gryshuk, A., Rittenhouse-Olson, K., Oseroff, A., and Pandey, R.K. Functionalization of OEP-Based Benzocholrins to Develop Galectin- Specific Photosensitizers for Photodynamic Therapy. J. Org. Chem. 69(1); 158-172. 2004.
 Sally A.Quataert , Kate Rittenhouse-Olson, Carol S. Kirch, Branda Hu, Shelley Secor, Nancy Strong, and Dace V. Madore. Assignment of Weight-Based Antibody Units for 13 Serotypes to a Human Anti- pneumococcal Standard Reference Serum, Lot 89-S. Clin. Diagn. Lab. Immunol. 2004 11: 1064-1069

 O. Kurtenkov, K. Klaamas, K. Rittenhouse-Olson L. Vahter, B. Sergejev, L. Miljukhina, L. Shljapnikova .   IgG Immune response to Tumor-Associated Carbohydrate Antigens (TF, Tn, alphaGal) in Patients with Breast Cancer: Impact of Neoadjuvant Chemotherapy and Relation to the Survival. Experimental Oncology 27, No 5 136-140. 2005

Jason Catania, Barbara McGarrigle, Kate Rittenhouse-Olson, and James Olson. Induction of CYP2B and CYP2E1 in Precision-Cut Rat Liver Slices Cultured in Defined Medium   Toxicology in Vitro. Vol. 21, No. 1, pages 109-115 (2007)

. Jamie Heimburg, Jun Yan, Susan Morey, Olga V. Glinskii, Virginia H. Huxley, Vladislav V. Glinsky, Linda Wild, Robert Klick, Rene Roy and Kate Rittenhouse- Olson    Therapeutic Potential of a Monoclonal Anti-T-Ag Antibody for Breast Carcinoma. Neoplasia feature article, cover photo volume 8 :11 939-948.

  R. Chaturvedi, J. Yan, J. Heimburg, S. Koury, M. Sajjad, and K. Rittenhouse-Olson. Immuno-PET and Biodistribution using Iodine- 124 labeled anti-Thomsen-Friedenreich-Antigen Monoclonal Antibody JAA-F11 Applied Radiation and Isotopes. In press.

Rittenhouse-Olson K. Jaa-f11: extending the life of mice with breast cancer. [Review] [34 refs] Expert Opinion on Biological Therapy. 7(7):923-8, 2007 Jul.

Catania JR. McCarrigle BP. Rittenhouse-Olson K. Olson JR. Induction of CYP2B and CYP2E1 in precision -cut rat liver slices cultured in defined medium. Toxicology in Vitro. 21(1):109-15, 2007 Feb.

Heimburg J. Yan J. Morey S. Glinskii OV. Huxley VH. Wild L. Klick R. Roy R. Glinsky VV. Rittenhouse-Olson K. Inhibitin of spontaneous breast cancer metastasis by anti-Thomsen-Friedenreich antigen monoclonal antibody JAA-F11. Neoplasia (New York). 8(11):939-48, 2006 Nov.