Journal of immunotherapy : official journal of the Society for Biological Therapy最新文献

{"title":"Human antibody response to the intravenous and intraperitoneal administration of the F(ab')2 fragment of the OC125 murine monoclonal antibody.","authors":"V E Maher,&nbsp;S J Drukman,&nbsp;R J Kinders,&nbsp;R E Hunter,&nbsp;J Jennings,&nbsp;C Brigham,&nbsp;S Stevens,&nbsp;T W Griffin","doi":"10.1097/00002371-199201000-00007","DOIUrl":"https://doi.org/10.1097/00002371-199201000-00007","url":null,"abstract":"<p><p>We have characterized the human immune response against murine monoclonal antibodies (HAMA) in 18 patients following administration of the F(ab')2 fragment of the murine monoclonal antibody OC125. OC125 is directed against the CA125 antigen, present on the surface of many human ovarian cancers. An affinity matrix was used to separate serum into immunoglobulin-containing and immunoglobulin-free fractions. HAMA titer was determined on the immunoglobulin fraction with an OC125 sandwich enzyme-linked immunosorbent assay (ELISA). All patients developed an HAMA response, despite the use of F(ab')2 fragments and small amounts (1-4 mg) of antibody. It may be that the intraperitoneal (i.p.) route provides a more marked HAMA response. Enzyme-linked sandwich immunoassays were also used to determine anti-isotype and anti-idiotype titers. Anti-isotype titers were analyzed with antigen irrelevant, isotype-matched murine antibodies and OC125-HRPO. Anti-idiotypes titers were assessed in a sandwich assay that utilized F(ab')2 and F(ab') fragments of OC125. The anti-isotype response tended to be of low titer and short duration, while the anti-idiotype response was of high titer and remarkably persistent. HAMA interfered in an unpredictable manner with the correct measurement of serum levels of CA125 in an enzyme immunoassay using OC125. Corrected values of CA125 could be obtained by measurement of antigen in the immunoglobulin-free fraction of serum. The response of one patient, who developed a markedly elevated anti-idiotype titer after serial i.v./i.p. injections, was further characterized and found to contain an antibody consistent with an anti-anti-idiotype to the CA125 antigen.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"11 1","pages":"56-66"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199201000-00007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12899114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoprothrombinemia associated with interleukin-2 therapy: correction with vitamin K.","authors":"G R Birchfield,&nbsp;G M Rodgers,&nbsp;K W Girodias,&nbsp;J H Ward,&nbsp;W E Samlowski","doi":"10.1097/00002371-199201000-00009","DOIUrl":"https://doi.org/10.1097/00002371-199201000-00009","url":null,"abstract":"<p><p>We noted that patients treated with high-dose interleukin (IL)-2 (600,000 IU/kg every 8 h by intravenous bolus) at our institution frequently developed prolongation of their prothrombin time (PT). We therefore performed a prospective study of coagulation function during IL-2 treatment. Since IL-2 treated individuals are known to develop cholestatic liver dysfunction, we hypothesized that the hypoprothrombinemia was due to deficiency of liver-synthesized clotting factors and could be prevented by vitamin K replacement. Alternating patients served as controls or received prophylactic subcutaneous subcutaneous vitamin K. While the nine control patients did not exhibit a significant increase (mean +/- SD) in PT (13.6 +/- 0.6 s pretreatment, 15.0 +/- 2.2 on day 4, and 15.0 +/- 2.5 on day 7, p = 0.77 by repeated measures analysis), three patients developed marked increases in PT (greater than 18 s). Changes in partial thromboplastin time (PTT) over this interval were also not statistically significant. Factor VII levels decreased in all patients from 106 +/- 22 to 59 +/- 16 and 52 +/- 26% on days 4 and 7 (p = 0.0002). Factor VII levels in four patients dropped below the lower limit of normal. Prophylactic treatment of seven patients with vitamin K on days 1-8 of the IL-2 therapy protocol resulted in diminished changes in PT and factor VII compared to control patients (p = 0.02 and 0.003 respectively). No vitamin K-treated patient developed PT or Factor VII levels significantly outside the normal range. Prophylactic vitamin K can prevent hypoprothrombinemia in patients treated with IL-2. This may be of importance in patients with decreased hepatic vitamin K stores, who may be at risk for bleeding complications.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"11 1","pages":"71-5"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199201000-00009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12899116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-fold expansion of human cytotoxic T-lymphocytes specific for autologous melanoma cells for use in immunotherapy.","authors":"F Jotereau,&nbsp;M C Pandolfino,&nbsp;D Boudart,&nbsp;E Diez,&nbsp;B Dreno,&nbsp;J Y Douillard,&nbsp;J Y Muller,&nbsp;B LeMevel","doi":"10.1097/00002371-199112000-00003","DOIUrl":"https://doi.org/10.1097/00002371-199112000-00003","url":null,"abstract":"<p><p>We set up a culture protocol that consistently allows high-fold expansion of tumor-specific T-lymphocytes from most melanoma-invaded biopsies with low doses of recombinant interleukin-2 (rIL-2). Between 2-60 x 10(6) T-lymphocytes could be obtained and cryopreserved from 12 out of 13 patients, by culturing only 50 mm3 tumor tissue with rIL-2. Thawed lymphocytes from 11 of these patients could then be expanded by a median factor of 32,800 by culturing them successively in microplates on irradiated feeder cells with rIL-2 for approximately 2 weeks and then in culture bags or flasks with only rIL-2 for 1-2 additional weeks. Dead feeder cells disappeared during the last phase of the lymphocyte culture with rIL-2. Interestingly, each time they were expanded under these conditions, tumor-infiltrating lymphocytes (TIL) or lymph-node lymphocytes developed a lytic activity apparently restricted to the autologous melanoma line. Tumor-specific lysis, which was maximum at around the end of T-lymphocyte expansion, ranged between 31-63% lysis at an effector:target (E:T) ratio of 20:1. This culture method would thus appear to be suitable for reliable production of over 10(10) T-lymphocytes with good tumor-specific lytic activity from most melanoma-invaded biopsy. It should permit analysis of the immunotherapeutic potential of these populations reinjected into cancer patients.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"10 6","pages":"405-11"},"PeriodicalIF":0.0,"publicationDate":"1991-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199112000-00003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12930807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comparison of the immunomodulating properties of two forms of monophosphoryl lipid A analogues.","authors":"A G Johnson,&nbsp;M A Tomai,&nbsp;Y F Chen,&nbsp;M Odean","doi":"10.1097/00002371-199112000-00002","DOIUrl":"https://doi.org/10.1097/00002371-199112000-00002","url":null,"abstract":"<p><p>This investigation compared the immunomodulating activities of two forms monophosphoryl lipid A, which are analogues of bacterial lipopolysaccharides with little or no toxicity. Tested were a synthetic compound designated 504 and a purified compound, isolated from bacterial cell walls designated MPL. Both of these clinical adjuvant candidates were effective in mice in exerting strong immunomodulating activity in the following areas: (a) enhancing antibody production in young and aging mice; (b) suppressing antibody formation under different experimental conditions; (c) activating macrophages to secrete interleukin 1, hydrogen peroxide, and superoxide anion; and (d) stimulating proliferation of spleen cells from C3H/HeN mice. Both exhibited considerably reduced toxicity in LD50 assays when compared to native lipopolysaccharides (LPS). The LD50 for MPL was 225 times and that of compound 504, 40 times that of native LPS in the exquisitely sensitive, galactosamine-loaded C57BL/6 murine strain.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"10 6","pages":"398-404"},"PeriodicalIF":0.0,"publicationDate":"1991-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199112000-00002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12930806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A phase I trial of 21-day continuous venous infusion of alpha-interferon at circadian rhythm modulated rate in cancer patients.","authors":"P Deprés-Brummer,&nbsp;F Levi,&nbsp;M Di Palma,&nbsp;A Beliard,&nbsp;P Lebon,&nbsp;S Marion,&nbsp;C Jasmin,&nbsp;J L Misset","doi":"10.1097/00002371-199112000-00008","DOIUrl":"https://doi.org/10.1097/00002371-199112000-00008","url":null,"abstract":"<p><p>The toxicity and/or the stimulation of natural killer cell activity that resulted from exposure to alpha-interferon varied according to circadian dosing time, both in mice and in human beings. Ten patients with advanced renal cell carcinoma or melanoma were treated with recombinant alpha-interferon-2b using a continuous 21-day intravenous schedule at circadian modulated rate. Patients received 15-20 MU/m2/day in an ambulatory care program. The drug was delivered via an external programmable-in-time pump. Thirty-nine courses of therapy were given (2-12 courses per patient). Severe side effects included World Health Organization grade III somnolence (one patient, 1 course) and grade III-IV neutropenia (five patients, 10 courses). Karnofsky performance status decreased by 40% in 3 patients (five courses). Two of these patients were withdrawn from the study because of toxicity. Disease was stabilized in four of the seven patients evaluable for response. Seven of the 10 patients are alive at 15 months' median follow-up. Two have continued with chronotherapy for 9+ and 13+ months, respectively. A large interpatient variability characterized the maximally tolerated dose. Two patients led their usual activities while receiving 20 MU/m2/day for three courses or more. Conversely, two patients exhibited severe side effects with 10 MU/m2/day. As compared with schedules of standard administration or continuous flat infusion, this circadian schedule of infusion allowed a large increment in total daily dose and dose intensity. A starting dose of 15 MU/m2/day was well tolerated by 8 of 10 patients and can be recommended using this circadian modulated schedule.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"10 6","pages":"440-7"},"PeriodicalIF":0.0,"publicationDate":"1991-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199112000-00008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12930743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiproliferative effect of interleukin-4 in B chronic lymphocytic leukemia.","authors":"H Y Luo,&nbsp;M Rubio,&nbsp;G Biron,&nbsp;G Delespesse,&nbsp;M Sarfati","doi":"10.1097/00002371-199112000-00005","DOIUrl":"https://doi.org/10.1097/00002371-199112000-00005","url":null,"abstract":"<p><p>Recombinant interleukin-4 (IL-4) profoundly inhibits the proliferative response of chronic lymphocytic leukemic B cells (B-CLLs) to recombinant interleukin-2 (IL-2). In the present study, we confirmed and extended these data by showing that IL-4 strongly suppresses the [3H]thymidine incorporation by B-CLLs stimulated by recombinant tumor necrosis factor alpha, recombinant interferon alpha, IL-2, and low molecular weight B cell growth factor in the absence of costimulant. Recombinant interleukin-4 inhibits spontaneous DNA synthesis suggesting that it also interferes with the autocrine proliferation of these cells. Kinetic studies indicate that IL-4 suppresses rather than shifts the peak of cytokine-induced DNA synthesis. Moreover, IL-4 blocks the progression of B-CLLs in or into G1 stage of the cell cycle as shown by the inhibition of cytokine-induced [3H]uridine incorporation. Finally, IL-4 pretreatment of B-CLLs prevents their subsequent proliferative response to the above cytokines, indicating that IL-4 confers to the B-CLLs a state of resistance to numerous stimulatory cytokines. The antiproliferative effects of IL-4 suggest that this lymphokine may have important therapeutic implications for the B-CLL patients.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"10 6","pages":"418-25"},"PeriodicalIF":0.0,"publicationDate":"1991-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199112000-00005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12930808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thyroid function abnormalities associated with the chronic outpatient administration of recombinant interleukin-2 and recombinant interferon-alpha.","authors":"E L Jacobs,&nbsp;M J Clare-Salzler,&nbsp;I J Chopra,&nbsp;R A Figlin","doi":"10.1097/00002371-199112000-00009","DOIUrl":"https://doi.org/10.1097/00002371-199112000-00009","url":null,"abstract":"<p><p>We prospectively examined thyroid function during and following chronic, outpatient therapy with recombinant interleukin-2 (rIL-2) and Roferon-A (rIFN-alpha 2a). Twenty-two of 30 patients with advanced renal cell carcinoma treated on a phase II open pilot study of concomitant rIL-2 and rIFN-alpha 2a were included. Serum levels of thyroxine, triiodothyronine, free thyroxine index, thyrotropin, antithyroid antibodies, and thyrotropin (TSH) receptor binding antibodies were measured before therapy and after every other cycle. Selected patients underwent studies after every cycle and following completion of therapy. Twenty patients (91%) developed laboratory evidence of thyroid dysfunction, 11 (50%) developed hypothyroidism, five (23%) had a biphasic pattern, and four (18%) had hyperthyroidism. The incidence of thyroid dysfunction increased with increased number of treatment cycles. Transient hyperthyroidism was noted in six of the 11 patients studied after the first cycle and persisted after cycle three in only two patients. Hypothyroidism was not observed after cycle 1, but became increasingly frequent between cycles 2 (56%) and 6 (90%). Thyroid function normalized following therapy in nine of 12 patients tested. Antithyroid antibodies were identified pretherapy in five patients (23%) and de novo in none; TSH receptor binding antibodies were not detected. This study demonstrates a remarkably high frequency of reversible thyroid dysfunction in patients with advanced renal cell carcinoma treated with repeated cycles of rIL-2 plus rIFN-alpha 2a. We conclude that chronic therapy with rIL-2 and rIFN-alpha 2a produces thyroid dysfunction in virtually all patients most likely secondary to a nonspecific, nonautoimmune, toxic manifestation of prolonged treatment. IL-2 therapy may, therefore, produce thyroid dysfunction by more than one mechanism.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"10 6","pages":"448-55"},"PeriodicalIF":0.0,"publicationDate":"1991-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199112000-00009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12930744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell surface expression of ICAM-1 (CD54) and LFA-3 (CD58), two adhesion molecules, is up-regulated on bone marrow leukemic blasts after in vivo administration of high-dose recombinant interleukin-2.","authors":"D Olive,&nbsp;M Lopez,&nbsp;D Blaise,&nbsp;P Viens,&nbsp;A M Stoppa,&nbsp;M Brandely,&nbsp;C Mawas,&nbsp;P Mannoni,&nbsp;D Maraninchi","doi":"10.1097/00002371-199112000-00004","DOIUrl":"https://doi.org/10.1097/00002371-199112000-00004","url":null,"abstract":"<p><p>High-dose recombinant interleukin-2 (rIL-2) therapy can induce long-term remission in patients with melanoma and renal and colon cancer. More recently, in vivo IL-2 therapy was shown to induce complete or partial remission in some cases of relapsed chemotherapy-resistant acute myeloid leukemia. We have investigated the phenotypic modifications of bone marrow cells obtained from five patients with acute myeloid leukemia in relapse receiving high-dose i.v. rIL-2. We found that, in three of five patients, IL-2 could induce, in vivo, an increase in the expression of CD54/ICAM-1 and to a lesser extent of CD58/LFA-3 on bone marrow leukemic blasts. This demonstrates that rIL-2 modifies directly or indirectly the expression of the cell surface molecules of the tumor cells themselves. Upregulation of such adhesion molecules could account for the enhancement of cell interactions between the tumor and effector cells such as T, natural killer, and phagocytic cells as well as being indicators of differentiation signaling.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"10 6","pages":"412-7"},"PeriodicalIF":0.0,"publicationDate":"1991-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199112000-00004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12886735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adoptively transferred tumor-infiltrating lymphocytes can cure established metastatic tumor in mice and persist long-term in vivo as functional memory T lymphocytes.","authors":"R B Alexander,&nbsp;S A Rosenberg","doi":"10.1097/00002371-199112000-00001","DOIUrl":"https://doi.org/10.1097/00002371-199112000-00001","url":null,"abstract":"<p><p>Tumor infiltrating lymphocytes (TILs) are derived from solid tumors by culturing single cell suspensions of the tumors in low dose interleukin-2 (IL-2) and intermittent tumor stimulation. We have investigated the survival of TILs after intravenous injection into tumor-bearing mice. Using several murine transplantable sarcomas, we examined the in vivo survival of TILs derived from B6.PL Thy 1a/CY mice (Thy-1.1), which were used to treat established experimental metastases in C57BL/6N (Thy-1.2) mice. Donor and host lymphoid cells could be clearly distinguished by fluorescence-activated cell sorting. We found that TILs or TILs + IL-2 could extend the survival of and, in some instances, cure established experimental hepatic and pulmonary metastases. Donor TILs could be recovered from treated animals at all time points tested; in mice cured of pulmonary metastases donor TILs could be detected as late as 119 days after intravenous injection even in the absence of exogenous IL-2. The administration of a relatively low dose of IL-2 in vivo to mice receiving TILs increased the number of donor TILs recovered from the lungs of cured animals 5-10-fold at all time points but did not change the period of time during which donor TILs could be detected in vivo. Additionally, TILs could be recovered from animals cured of established metastases and such cells retained their antitumor activity in vivo. Finally, when mice cured of pulmonary metastases by TILs or TILs + IL-2 were rechallenged with tumor, donor TILs specifically accumulated at the site of tumor rechallenge up to 4 months after adoptive transfer of TILs.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"10 6","pages":"389-97"},"PeriodicalIF":0.0,"publicationDate":"1991-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199112000-00001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12930805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase I trial of continuous infusion interleukin-2 and doxorubicin in patients with refractory malignancies.","authors":"R M Bukowski,&nbsp;J S Sergi,&nbsp;G T Budd,&nbsp;S Murthy,&nbsp;R Tubbs,&nbsp;V Gibson,&nbsp;L Bauer,&nbsp;J Stanley,&nbsp;S Gautam,&nbsp;J Finke","doi":"10.1097/00002371-199112000-00007","DOIUrl":"https://doi.org/10.1097/00002371-199112000-00007","url":null,"abstract":"<p><p>A phase I trial was performed to assess the immunomodulatory activities, maximum tolerated doses, and the toxicity of recombinant interleukin-2 (rIL-2) administered in combination with doxorubicin to patients with refractory malignancies. Therapy was administered to successive cohorts of four to six patients who were treated at three different dose levels (1A, 1B, 2A). Levels 1-2 refer to doxorubicin (40 or 60 mg/m2) given as an intravenous (i.v.) bolus on day 1, and levels A-B refer to rIL-2 (1.0 or 3.0 x 10(6) U/m2) given as a continuous i.v. infusion on days 2-5, 9-12, and 16-19. Cycles were repeated every 28 days. Seventeen patients were entered in the trial. Dose limiting toxicity consisted of neutropenia, and the maximum tolerated dose (MTD) of the combination was doxorubicin 40 mg/m2 and rIL-2 3.0 x 10(6) U/m2. No objective responses were observed. Lymphocytosis related to rIL-2 occurred and flow cytometry demonstrated significant increases in the following subsets: CD3+CD25+HLADr+ and CD11b-CD16c+CD8-. Natural killer cell activity and lymphokine-activated killer (LAK) cell precursors were increased in patients treated at dose levels 1A and 1B (40 mg/m2 doxorubicin), but no consistent changes in LAK activity were noted. No clinical responses were seen and the overall toxicity of this combination was moderate to severe. Administration of doxorubicin prior to rIL-2 does not enhance the immunologic effects of rIL-2.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"10 6","pages":"432-9"},"PeriodicalIF":0.0,"publicationDate":"1991-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199112000-00007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12930810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}