| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Advances in Brief |
Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts 02115 [M. J. R., C. C., J. R.]; Tupper Research Institute and Division of Hematology/Oncology, Tufts-New England Medical Center, Boston, Massachusetts 02111 [M. B. A.]; Division of Hematology/Oncology, Indiana University Medical Center, Indianapolis, Indiana 46202 [M. S. G.]; Division of Surgical Oncology, Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15261 [M. T. L.]; and Genetics Institute, Cambridge, Massachusetts 02140 [M. L. S.]
The immunological effects of recombinant human interleukin 12 (rhIL-12) administration were examined during the conduct of a Phase I clinical trial. Forty patients with advanced cancer received bolus i.v. injections of rhIL-12 in doses ranging between 3 and 1000 ng/kg. Dose-dependent increases in serum IFN-
levels were seen during rhIL-12 therapy. Significant lymphopenia was observed 24 h after single i.v. injections of rhIL-12 at each dose level. The degree of lymphopenia was dose dependent, and a plateau effect was seen with rhIL-12 doses of 100 ng/kg and higher. Lymphocyte counts reached nadir levels at approximately 10 h after rhIL-12 injection and returned to baseline within 14 days postinjection. Rebound lymphocytosis, as seen after interleukin 2 therapy, was not observed after recovery from rhIL-12-induced lymphopenia. rhIL-12-induced lymphopenia involved all major lymphocyte subsets, although natural killer (NK) cell numbers were the most profoundly affected, and CD4 T-cell numbers were the least affected. CD2, LFA-1, and CD56 were transiently up-regulated on the surface of NK cells exposed to rhIL-12 in vivo. Peripheral blood mononuclear cells obtained from cancer patients before rhIL-12 therapy exhibited defective NK cell cytotoxicity and T-cell-proliferative responses. Peripheral blood mononuclear cells obtained after lymphocyte recovery following the administration of a single 500 ng/kg dose of rhIL-12 displayed augmented NK cell cytolytic activity in four of four patients tested and enhanced T-cell proliferation in three of four patients tested. These studies confirm that doses of rhIL-12 resulting in significant immunological activity can be administered with acceptable toxicity to cancer patients. Furthermore, rhIL-12 therapy can reverse defects in NK cell and T-cell function that are associated with advanced cancer in humans.
This article has been cited by other articles:
|
|
 |
|
  M. J. Robertson, J. W. Mier, T. Logan, M. Atkins, H. Koon, K. M. Koch, S. Kathman, L. N. Pandite, C. Oei, L. C. Kirby, et al. Clinical and biological effects of recombinant human interleukin-18 administered by intravenous infusion to patients with advanced cancer. Clin. Cancer Res., July 15, 2006; 12(14): 4265 - 4273. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Trudeau, M. M. Cotreau, L. Stonis, K. H. Dykstra, J. L. Oestreicher, A. Strahs, A. J. Dorner, V. H. Van Cleave, W. L. Trepicchio, and U. S. Schwertschlag A Single Administration of Recombinant Human Interleukin-12 Is Associated With Increased Expression Levels of Interferon-gamma and Signal Transducer and Activator of Transcription in Healthy Subjects J. Clin. Pharmacol., June 1, 2005; 45(6): 649 - 658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M.L. van Herpen, J. A.W.M. van der Laak, I. J. M. de Vries, J. H. van Krieken, P. C. de Wilde, M. G.J. Balvers, G. J. Adema, and P. H.M. De Mulder Intratumoral Recombinant Human Interleukin-12 Administration in Head and Neck Squamous Cell Carcinoma Patients Modifies Locoregional Lymph Node Architecture and Induces Natural Killer Cell Infiltration in the Primary Tumor Clin. Cancer Res., March 1, 2005; 11(5): 1899 - 1909. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. B. Dickerson, N. Akhtar, H. Steinberg, Z.-Y. Wang, M. J. Lindstrom, M. L. Padilla, R. Auerbach, and S. C. Helfand Enhancement of the Antiangiogenic Activity of Interleukin-12 by Peptide Targeted Delivery of the Cytokine to {alpha}v{beta}3 Integrin Mol. Cancer Res., December 1, 2004; 2(12): 663 - 673. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Younes, B. Pro, M. J. Robertson, I. W. Flinn, J. E. Romaguera, F. Hagemeister, N. H. Dang, P. Fiumara, E. M. Loyer, F. F. Cabanillas, et al. Phase II Clinical Trial of Interleukin-12 in Patients with Relapsed and Refractory Non-Hodgkin's Lymphoma and Hodgkin's Disease Clin. Cancer Res., August 15, 2004; 10(16): 5432 - 5438. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Parihar, P. Nadella, A. Lewis, R. Jensen, C. De Hoff, J. E. Dierksheide, A. M. VanBuskirk, C. M. Magro, D. C. Young, C. L. Shapiro, et al. A Phase I Study of Interleukin 12 with Trastuzumab in Patients with Human Epidermal Growth Factor Receptor-2-Overexpressing Malignancies: Analysis of Sustained Interferon {gamma} Production in a Subset of Patients Clin. Cancer Res., August 1, 2004; 10(15): 5027 - 5037. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Salem, A. N. Kadima, Y. Zhou, C. L. Nguyen, M. P. Rubinstein, M. Demcheva, J. N. Vournakis, D. J. Cole, and W. E. Gillanders Paracrine Release of IL-12 Stimulates IFN-{gamma} Production and Dramatically Enhances the Antigen-Specific T Cell Response after Vaccination with a Novel Peptide-Based Cancer Vaccine J. Immunol., May 1, 2004; 172(9): 5159 - 5167. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. van Herpen, M. Looman, M. Zonneveld, N. Scharenborg, P. C. de Wilde, L. van de Locht, M. A. W. Merkx, G. J. Adema, and P. H. De Mulder Intratumoral Administration of Recombinant Human Interleukin 12 in Head and Neck Squamous Cell Carcinoma Patients Elicits a T-Helper 1 Profile in the Locoregional Lymph Nodes Clin. Cancer Res., April 15, 2004; 10(8): 2626 - 2635. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Pelloso, K. Cyran, L. Timmons, B. T. Williams, and M. J. Robertson Immunological Consequences of Interleukin 12 Administration after Autologous Stem Cell Transplantation Clin. Cancer Res., March 15, 2004; 10(6): 1935 - 1942. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Satoh, T. Saika, S. Ebara, N. Kusaka, T. L. Timme, G. Yang, J. Wang, V. Mouraviev, G. Cao, E. M. A. Fattah, et al. Macrophages Transduced with an Adenoviral Vector Expressing Interleukin 12 Suppress Tumor Growth and Metastasis in a Preclinical Metastatic Prostate Cancer Model Cancer Res., November 15, 2003; 63(22): 7853 - 7860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. van Herpen, R. Huijbens, M. Looman, J. de Vries, H. Marres, J. van de Ven, R. Hermsen, G. J. Adema, and P. H. De Mulder Pharmacokinetics and Immunological Aspects of a Phase Ib Study with Intratumoral Administration of Recombinant Human Interleukin-12 in Patients with Head and Neck Squamous Cell Carcinoma: A Decrease of T-bet in Peripheral Blood Mononuclear Cells Clin. Cancer Res., August 1, 2003; 9(8): 2950 - 2956. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ribas, L. H. Butterfield, J. A. Glaspy, and J. S. Economou Current Developments in Cancer Vaccines and Cellular Immunotherapy J. Clin. Oncol., June 15, 2003; 21(12): 2415 - 2432. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Leong, J. C. C. Chang, R. Ong, G. Dawes, W. P. C. Stemmer, and J. Punnonen Optimized expression and specific activity of IL-12 by directed molecular evolution PNAS, February 4, 2003; 100(3): 1163 - 1168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. D. Davis, M. Jefford, P. Parente, and J. Cebon Rational approaches to human cancer immunotherapy J. Leukoc. Biol., January 1, 2003; 73(1): 3 - 29. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. A. Portielje, C. H. J. Lamers, W. H. J. Kruit, A. Sparreboom, R. L. H. Bolhuis, G. Stoter, C. Huber, and J. W. Gratama Repeated Administrations of Interleukin (IL)-12 Are Associated with Persistently Elevated Plasma Levels of IL-10 and Declining IFN-{gamma}, Tumor Necrosis Factor-{alpha}, IL-6, and IL-8 Responses Clin. Cancer Res., January 1, 2003; 9(1): 76 - 83. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Robertson, D. Pelloso, R. Abonour, R. A. Hromas, R. P. Nelson Jr., L. Wood, and K. Cornetta Interleukin 12 Immunotherapy after Autologous Stem Cell Transplantation for Hematological Malignancies Clin. Cancer Res., November 1, 2002; 8(11): 3383 - 3393. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Robertson Role of chemokines in the biology of natural killer cells J. Leukoc. Biol., February 1, 2002; 71(2): 173 - 183. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. P. Bradney, G. D. Sempowski, H.-X. Liao, B. F. Haynes, and H. F. Staats Cytokines as Adjuvants for the Induction of Anti-Human Immunodeficiency Virus Peptide Immunoglobulin G (IgG) and IgA Antibodies in Serum and Mucosal Secretions after Nasal Immunization J. Virol., January 15, 2002; 76(2): 517 - 524. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Ansell, T. E. Witzig, P. J. Kurtin, J. A. Sloan, D. F. Jelinek, K. G. Howell, S. N. Markovic, T. M. Habermann, G. G. Klee, P. J. Atherton, et al. Phase 1 study of interleukin-12 in combination with rituximab in patients with B-cell non-Hodgkin lymphoma Blood, January 1, 2002; 99(1): 67 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gorschluter, C. Ziske, A. Glasmacher, and I. G. H. Schmidt-Wolf Current Clinical and Laboratory Strategies to Augment the Efficacy of Immunotherapy in Multiple Myeloma Clin. Cancer Res., August 1, 2001; 7(8): 2195 - 2204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. S. Wang, E. Zorn, and J. Ritz Specific down-regulation of interleukin-12 signaling through induction of phospho-STAT4 protein degradation Blood, June 15, 2001; 97(12): 3860 - 3866. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Mortarini, A. Borri, G. Tragni, I. Bersani, C. Vegetti, E. Bajetta, S. Pilotti, V. Cerundolo, and A. Anichini Peripheral Burst of Tumor-specific Cytotoxic T Lymphocytes and Infiltration of Metastatic Lesions by Memory CD8+ T Cells in Melanoma Patients Receiving Interleukin 12 Cancer Res., July 1, 2000; 60(13): 3559 - 3568. [Abstract] [Full Text]
|
|
|
|
|
|
N. K. Egilmez, Y. S. Jong, M. S. Sabel, J. S. Jacob, E. Mathiowitz, and R. B. Bankert In Situ Tumor Vaccination with Interleukin-12-encapsulated Biodegradable Microspheres: Induction of Tumor Regression and Potent Antitumor Immunity Cancer Res., July 1, 2000; 60(14): 3832 - 3837. [Abstract] [Full Text]
|
|
|
|
|
|
R. Ohno, Y. Yamaguchi, T. Toge, T. Kinouchi, T. Kotake, M. Shibata, Y. Kiyohara, S. Ikeda, I. Fukui, A. Gohchi, et al. A Dose-Escalation and Pharmacokinetic Study of Subcutaneously Administered Recombinant Human Interleukin 12 and Its Biological Effects in Japanese Patients with Advanced Malignancies Clin. Cancer Res., July 1, 2000; 6(7): 2661 - 2669. [Abstract] [Full Text]
|
|
|
|
|
|
K. S. Wang, D. A. Frank, and J. Ritz Interleukin-2 enhances the response of natural killer cells to interleukin-12 through up-regulation of the interleukin-12 receptor and STAT4 Blood, May 15, 2000; 95(10): 3183 - 3190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Gollob, J. W. Mier, K. Veenstra, D. F. McDermott, D. Clancy, M. Clancy, and M. B. Atkins Phase I Trial of Twice-Weekly Intravenous Interleukin 12 in Patients with Metastatic Renal Cell Cancer or Malignant Melanoma: Ability to Maintain IFN-{{gamma}} Induction Is Associated with Clinical Response Clin. Cancer Res., May 1, 2000; 6(5): 1678 - 1692. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
