A novel CD44v6 targeting antibody fragment with improved tumor-to-blood ratio

The chimeric monoclonal antibody U36 (cMAb U36) recognizes the CD44v6 antigen. Its potential as a radioimmunotargeting agent, as well as its safety, has been shown in previous studies in head and neck cancer patients. However, intact MAbs have long circulation time in the blood and tumor targeting may also be hampered due to the slow and incomplete diffusion into solid tumors. In comparison, smaller monovalent Fab' and divalent F(ab')2 fragments are expected to exhibit shorter circulating half-lives, better tumor penetration and are thus more likely to yield better imaging results. In this study, novel F(ab')2 and Fab' fragments from cMAb U36 were radiolabeled with 125I and the characteristics of the conjugates in vitro were examined. The biodistribution of the conjugates were then evaluated in nude mice bearing CD44v6-expressing xenograft tumors. Furthermore, the penetration depth and distribution in tumor tissue was assessed by autoradiography in selected tumor samples. The in vitro experiments showed that the conjugates were stable and had intact affinity to CD44v6. The biodistribution study demonstrated superior tumor-to-blood ratio for the novel cMAb U36 fragment 125I-F(ab')2 compared with both the intact MAb and the monovalent fragment form. Autoradiography also revealed better tumor penetration for 125I-F(ab')2. This study demonstrates that the use of antibody fragments may improve radioimmunotargeting and possibly improve the management of head and neck malignancies.

Haylock, Anna-KarinUppsala universitet,Öron-, näs- och halssjukdomar(Swepub:uu)annha659 (author)
Spiegelberg, DianaUppsala universitet,Enheten för biomedicinsk strålningsvetenskap(Swepub:uu)diasp673 (author)
Qvarnström, FredrikUppsala universitet,Enheten för onkologi(Swepub:uu)frqva367 (author)
Wester, KennethUppsala universitet,Molekylär och morfologisk patologi,Enheten för biomedicinsk strålningsvetenskap(Swepub:uu)kennwest (author)
Nestor, Marika,1976-Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Öron-, näs- och halssjukdomar,Head & Neck Tumor Targeting(Swepub:uu)manes424 (author)
Uppsala universitetÖron-, näs- och halssjukdomar (creator_code:org_t)

In:International Journal of Oncology: Spandidos Publications40:5, s. 1525-15321019-64391791-2423

By the author/editor: Sandström, Karl; Haylock, Anna-Ka ...; Spiegelberg, Dia ...; Qvarnström, Fred ...; Wester, Kenneth; Nestor, Marika, ...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Medical Biotechn ...; and Medical Biotechn ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Otorhinolaryngol ...

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