Abstract
Antibody (Ab)-based tumor therapeutics use the tumor-binding specificity of the Ab to target Fc functions or associated molecules to the site of the tumor. We have used an Ab-interleukin-2 (IL-2) fusion protein to deliver IL- 2 to a murine B cell lymphoma (38C13). This anti-Id IgG3-C(H)3-IL-2, which recognizes the idiotype present on the surface of the lymphoma has a half- life in mice approximately 17-fold longer than the half-life reported for IL- 2. Gamma camera studies showed that anti-Id IgG3-C(H)3-IL-2 localizes at the site of a subcutaneous tumor in mice. The anti-Id IgG3-C(H)3-IL-2 also shows enhanced antitumor activity compared with the combination of Ab and IL-2 administered together. However, the mechanism of antitumor activity appears to depend on the dose and the treatment schedule used. A single dose of fusion protein prevented tumor in only 50% of the animals, although all the survivors showed some evidence of immunologic memory. Although multiple doses are more effective in preventing tumor growth (87% survivors), they are ineffective in generating protective immunologic memory. Our results suggest that Ab-IL-2 fusion proteins will be useful in the diagnosis and treatment of human B cell lymphomas and other related malignancies.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 597-607 |
| Number of pages | 11 |
| Journal | Journal of Interferon and Cytokine Research |
| Volume | 18 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 1998 |
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All Science Journal Classification (ASJC) codes
- Immunology
- Cell Biology
- Virology
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An IgG3-IL-2 fusion protein recognizing a murine B cell lymphoma exhibits effective tumor imaging and antitumor activity. / Penichet, Manuel L.; Harvill, Eric T.; Morrison, Sherie L.
In: Journal of Interferon and Cytokine Research, Vol. 18, No. 8, 08.1998, p. 597-607.Research output: Contribution to journal › Article
TY - JOUR
T1 - An IgG3-IL-2 fusion protein recognizing a murine B cell lymphoma exhibits effective tumor imaging and antitumor activity
AU - Penichet, Manuel L.
AU - Harvill, Eric T.
AU - Morrison, Sherie L.
PY - 1998/8
Y1 - 1998/8
N2 - Antibody (Ab)-based tumor therapeutics use the tumor-binding specificity of the Ab to target Fc functions or associated molecules to the site of the tumor. We have used an Ab-interleukin-2 (IL-2) fusion protein to deliver IL- 2 to a murine B cell lymphoma (38C13). This anti-Id IgG3-C(H)3-IL-2, which recognizes the idiotype present on the surface of the lymphoma has a half- life in mice approximately 17-fold longer than the half-life reported for IL- 2. Gamma camera studies showed that anti-Id IgG3-C(H)3-IL-2 localizes at the site of a subcutaneous tumor in mice. The anti-Id IgG3-C(H)3-IL-2 also shows enhanced antitumor activity compared with the combination of Ab and IL-2 administered together. However, the mechanism of antitumor activity appears to depend on the dose and the treatment schedule used. A single dose of fusion protein prevented tumor in only 50% of the animals, although all the survivors showed some evidence of immunologic memory. Although multiple doses are more effective in preventing tumor growth (87% survivors), they are ineffective in generating protective immunologic memory. Our results suggest that Ab-IL-2 fusion proteins will be useful in the diagnosis and treatment of human B cell lymphomas and other related malignancies.
AB - Antibody (Ab)-based tumor therapeutics use the tumor-binding specificity of the Ab to target Fc functions or associated molecules to the site of the tumor. We have used an Ab-interleukin-2 (IL-2) fusion protein to deliver IL- 2 to a murine B cell lymphoma (38C13). This anti-Id IgG3-C(H)3-IL-2, which recognizes the idiotype present on the surface of the lymphoma has a half- life in mice approximately 17-fold longer than the half-life reported for IL- 2. Gamma camera studies showed that anti-Id IgG3-C(H)3-IL-2 localizes at the site of a subcutaneous tumor in mice. The anti-Id IgG3-C(H)3-IL-2 also shows enhanced antitumor activity compared with the combination of Ab and IL-2 administered together. However, the mechanism of antitumor activity appears to depend on the dose and the treatment schedule used. A single dose of fusion protein prevented tumor in only 50% of the animals, although all the survivors showed some evidence of immunologic memory. Although multiple doses are more effective in preventing tumor growth (87% survivors), they are ineffective in generating protective immunologic memory. Our results suggest that Ab-IL-2 fusion proteins will be useful in the diagnosis and treatment of human B cell lymphomas and other related malignancies.
UR - http://www.scopus.com/inward/record.url?scp=0031870775&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031870775&partnerID=8YFLogxK
U2 - 10.1089/jir.1998.18.597
DO - 10.1089/jir.1998.18.597
M3 - Article
C2 - 9726441
AN - SCOPUS:0031870775
VL - 18
SP - 597
EP - 607
JO - Journal of Interferon and Cytokine Research
JF - Journal of Interferon and Cytokine Research
SN - 1079-9907
IS - 8
ER -