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Biomedical subjects

J A Hank

Publications and source records attributed to J A Hank.

At least 37 records · Page 2Linked to original sources
PubMed1995

Clinical and immunological effects of treatment with murine anti-CD3 monoclonal antibody along with interleukin 2 in patients with cancer.

Anti-CD3 mAb and interleukin 2 (IL-2) were used in a Phase I study to treat 29 patients with cancer. The anti-CD3 was given as an i.v. bolus infusion over 10 min followed by two i.v. 96-h continuous infusions of IL-2 at 3 x 10(6) units/m2/day with a 3-day rest between the IL-2 infusions. Four patients were treated with 6, 18, 60, and 300 microgram/m2 anti-CD3. One patient received 3000 microgram/m2 anti-CD3. This patient developed profound hypotension and the IL-2 infusions were delayed for 2 weeks. Two patients were treated at an intermediate dose of 600 microgram/m2. These patients developed dose-limiting toxicities including hypotension, dyspnea and increased blood urea nitrogen, creatinine, and bilirubin. They were unable to complete their first course of therapy. In an effort to achieve a dose of anti-CD3 which would activate T cells in vivo, pentoxifylline was given to blunt the toxicities seen with anti-CD3 thought to be due predominantly to the cytokine syndrome and tumor necrosis factor release. Four patients received p.o. pentoxifylline to cover an anti-CD3 dose of 600 microgram/m2. The IL-2 infusion was initiated 1 week after the mAb. While there was an anti-CD3 dose-dependent increase in serum tumor necrosis factor level 1 h after mAb infusion, pentoxifylline did not reduce the serum tumor necrosis factor level. There was also an anti-CD3 dose-dependent increase in the serum soluble IL-2 receptor levels. Other immune parameters monitored, including in vitro cytotoxic and proliferative responses and lymphocyte count, were similar to treatment courses with IL-2 alone. Fourteen of 26 patients examined developed human anti-murine antibodies following a single dose of anti-CD3. There were no objective antitumor responses. We conclude that in vivo treatment with anti-CD3 did not enhance T cell activity or expansion with subsequent IL-2 infusion and that the combination of anti-CD3 followed by IL-2 did not improve upon the antitumor activity previously seen with IL-2 alone.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1994

Allogeneic T-cell clones able to selectively destroy Philadelphia chromosome-bearing (Ph1+) human leukemia lines can also recognize Ph1- cells from the same patient.

Immunocompetent cells in bone marrow allografts have been associated with a graft-versus-leukemia (GVL) effect. To further characterize effector mechanisms that may be involved in this GVL phenomenon, we have previously established an in vitro model to identify allogeneic T-cell clones that selectively mediate cytotoxicity against a patient's leukemic cells, but not against nonleukemic lymphocytes from the same patient. We have modified this in vitro model to test whether the Ph1 chromosome and the P210 fusion protein it controls have a detectable role in leukemia-specific recognition by allogeneic T-cell clones. In this report, T-cell lines reactive with allogeneic Ph1 chromosome-bearing (Ph1+) chronic myeloid leukemia (CML) cell lines were derived and selected to be minimally reactive with Ph1 negative (Ph1-) lymphoid lines from the same patient. However, after prolonged culture, these same T-cell lines also mediated significant destruction of the Ph1- target cells from the same patients. These T-cell lines specifically recognized cells from the allogeneic CML patient to which they were sensitized, and were not contaminated by an outgrowth of natural killer cells. Furthermore, subclones could be derived from these T-cell lines, and some of these subclones again showed selective killing of the allogeneic Ph1+ leukemia cell lines, and not of the Ph1- cell line from the same patient. Analyses of T-cell receptor (TCR) genes showed the alloreactive T-cell lines and the Ph1+ selective subclones derived from them to be of the same clonal origin. This suggests that the same T cells reacting with antigens expressed on the nonleukemic Ph1- targets can at times selectively and preferentially kill the allogeneic Ph1+ cells. As the same TCR that recognizes Ph1+ cells also can recognize the Ph1- targets, it appears that the Ph1+ chromosome does not play a detectable role in recognition by these allogeneic T-cell clones. This in vitro observation may provide a model for evaluating the relationship between GVL and graft-versus-host disease effects.

CD4 Antigens↗
PubMed1994

Clinical and immunological effects of human recombinant interleukin-2 given by repetitive weekly infusion to normal dogs.

Four normal adult dogs received two consecutive weekly cycles of human recombinant interleukin-2 (IL-2) by continuous infusion for 4 days/week. The dose of IL-2 given to each dog was 3 x 10(6) units m-2 day-1. Toxicities consisted of mild vomiting, diarrhea, and lethargy to varying degrees in all the dogs. These side-effects were reversed when the treatment was discontinued. Fever, tachypnea, and weight gain were not seen. A marked lymphocytosis and eosinophilia developed in all dogs after completion of each course of IL-2 (resulting in a more than sevenfold increase in each cell type) and persisted for more than 1 month in some. Fresh peripheral blood lymphocytes (PBL) obtained during this lymphocytosis mediated enhanced in vitro lysis of a natural-killer-cell-sensitive canine tumor cell line (CTAC). The in vitro proliferative responses of these same PBL to IL-2 could be detected earlier, progressed faster, and involved more cells than PBL tested prior to IL-2 infusion. Thus, a relatively well-tolerated regime of IL-2 in dogs can induce dramatic increases in lymphocyte numbers and activation, which is associated with augmentation of their in vitro antitumor reactivity. The clinical effectiveness of this immunotherapeutic approach remains to be tested in tumor-bearing dogs where it could serve as a relevant large-animal model for immunotherapy of cancer with IL-2.

Adenocarcinoma↗
PubMed1994

Induction of lymphokine-activated killer (LAK) activity in canine lymphocytes with low dose human recombinant interleukin-2 in vitro.

Interleukin-2 (IL-2) is an immunostimulatory cytokine that induces activation of peripheral blood lymphocytes (PBL) which can mediate augmented tumor cytotoxicity. Several regimens using IL-2 as treatment for metastatic melanoma and renal carcinoma have shown measurable tumor responses in 10-20% of human patients. Our overall goals are to determine the efficacy of IL-2 as an adjuvant treatment for canine tumors. In order to evaluate the possibility to extend the use of IL-2 in vivo in the dog, we examined the ability of a clinically relevant (low) dose of human recombinant IL-2 (100 units/ml) to enhance the tumoricidal properties of canine PBL in vitro. This was particularly important considering the need to establish the effects on canine PBL by IL-2 at a dose that is potentially achievable in vivo with acceptable side effects. Our data show, for the first time, the ability to separate canine natural killer (NK) cell activity from lymphokine-activated killer (LAK) cell activity (induced with a low IL-2 dose) mediated by canine PBL against two canine cell lines (CTAC and CML-10) used as targets in 4 vs. 16 hour killing assays. LAK cells generated by stimulation of canine PBL with 100 units/ml of IL-2 for 72 hours, could kill CTAC or CML-10 targets up to 11 or 18 times more efficiently, respectively, than fresh PBL in a 4 hour assay. However, the killing of efficiency of the LAK cells was only 2- to 3-fold greater than that of the fresh PBL in a 16 hour assay. This apparent reduction in the killing efficiency of the LAK cells was mostly due to increased spontaneous NK activity by the fresh PBL after 16 hours in culture; both the LAK cells and the fresh PBL (NK cells) mediated a greater overall cytotoxicity after 16 hours than they did in the 4 hour assays. These results indicate that a low dose of human recombinant IL-2 can augment tumor killing by canine PBL in vitro, and suggest that it may be feasible to examine the potential use of IL-2 as an immunotherapeutic agent in tumor-bearing dogs.

Adenocarcinoma↗
PubMed1994

Treatment of neuroblastoma patients with antiganglioside GD2 antibody plus interleukin-2 induces antibody-dependent cellular cytotoxicity against neuroblastoma detected in vitro.

Therapy of neuroblastoma patients with interleukin (IL)-2 activates effector cells capable of lysing tumor cells in vitro. When tumor cells are pretreated with certain monoclonal antibodies (MoAb), these in vivo activated effectors show augmented tumor lysis via antibody-dependent cellular cytotoxicity (ADCC). This study presents immunological analyses of serial blood samples from two refractory neuroblastoma patients who received combined in vivo therapy with murine anti-ganglioside GD2 monoclonal antibody 14.G2a and IL-2. These studies were designed to determine whether conditions that induce ADCC in vitro can be generated in vivo by combined therapy with IL-2 and MoAb. As shown previously, administration of IL-2 dramatically augments the ability of peripheral blood mononuclear cells (PBMC) to mediate ADCC. In addition, we demonstrate here that sera, obtained 1 h after infusion of 14.G2a, provides an effective source of functional antibody for ADCC mediated by PBMC from healthy donors. Finally, effective ADCC-mediated killing of neuroblastoma target cells was also achieved in vitro following IL-2 plus 14.G2a treatment when patients' effector cells were combined with patients' serum, as the source of 14.G2a antibody. These results indicate that this combination of IL-2 and 14.G2a generates conditions within the peripheral blood of pediatric neuroblastoma patients that enable their own lymphocytes to mediate antibody-dependent cellular cytotoxicity sufficient to effectively kill neuroblastoma cells in vitro.

Antibodies, Monoclonal↗
PubMed1994

Potential to involve multiple effector cells with human recombinant interleukin-2 and antiganglioside monoclonal antibodies in a canine malignant melanoma immunotherapy model.

Human tumors originating from neuroectodermal cells such as malignant melanoma and neuroblastoma express high levels of disialogangliosides GD2 and GD3, making these antigens ideal for targeting by monoclonal antibodies (Mabs). The purpose of this study was to investigate expression and targeting of gangliosides on canine melanoma. Using immunohistochemical methods, we analyzed the expression of disialogangliosides GD2 and GD3 on canine oral malignant melanomas with murine Mabs 14.G2a and R24 that recognize GD2 and GD3 disialogangliosides, respectively, on human tumors. We also assessed the ability of Mab 14.G2a (and its mouse-human chimera, ch 14.18) to mediate antibody-dependent cellular cytotoxicity (ADCC) in vitro against a canine malignant melanoma cell line with human recombinant interleukin-2 (IL-2) activated canine peripheral blood lymphocytes (PBL), or canine neutrophil effector cells. Our data show that Mabs 14.G2a and R24 recognized fresh frozen canine oral melanoma. Mabs 14.G2a or ch 14.18, or IL-2, potentiated lysis of the canine malignant melanoma cell line by canine PBL. The killing effect observed using the combination of either Mab with IL-2 was additive. Mab 14.G2a mediated potent ADCC of canine melanoma by canine neutrophils. These studies indicate that disialogangliosides are expressed on fresh canine melanoma cells. Mabs reactive with these antigens can target and trigger tumor killing by multiple canine effector populations and IL-2 can potentiate these effects by canine lymphocytes. Thus, canine oral malignant melanoma, a spontaneously occurring, metastatic cancer in the dog, may be a relevant animal model to investigate combination immunotherapy using antitumor Mab and IL-2.

Animals↗
PubMed1993

Modulation of target-cell culture conditions alters susceptibility to lymphocyte-mediated lysis.

The culture conditions of the immortalized human breast cell line, 184B5, can be manipulated to evaluate conditions that influence target lysis by activated immune effector cells. Exponentially growing 184B5 cells (EXP) are more susceptible than growth-factor-deprived (removal of epidermal growth factor and bovine pituitary extract) 184B5 cells (GFD) to lysis by lymphokine-activated killer (LAK) cells, activated natural killer (NK) clones, and activated gamma/delta receptor expressing T-cell clones. LAK-cell lysis of contact-inhibited 184B5 cells is similar to lysis of GFD, while 184B5 cells with severe nutrient deprivation are more easily lysed than GFD by LAK cells. In a cold target inhibition assay with LAK effector populations, EXP are better inhibitors than GFD against several targets. Further analysis of the mechanism by which changes of in vitro culture conditions alter target-cell susceptibility to immune-mediated lysis may assist therapeutic strategies that involve combinations of standard therapies with biologic approaches.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1993

A pilot phase II trial of continuous-infusion interleukin-2 followed by lymphokine-activated killer cell therapy and bolus-infusion interleukin-2 in renal cancer.

Nine patients with metastatic renal cell carcinoma were entered into a pilot protocol including a 4-week regimen utilizing human recombinant interleukin-2 (IL-2) and in vitro lymphokine-activated killer (LAK) cells. The regimen included 2 weeks (4 days of treatment and 3 days of rest/week) of continuous-infusion (c.i.) IL-2 at 3 x 10(6) U/m2/day, followed by two leukaphereses. LAK cells were cultured in vitro for 48 to 72 h and administered as a single infusion, followed by 9 days of bolus i.v. injections of 10(6) U IL-2/m2/dose, given every 8 hours (t.i.d.). The average (+/- SD) number of LAK cells infused per patient was 7.2 x 10(10) (+/- 3.5 x 10(10)). One patient showed > 50% shrinkage of tumor (lung + renal bed recurrence). Toxicity was similar to that encountered in other studies using similar IL-2 doses and LAK cells and consisted of fever, hypotension, fluid retention, and reversible renal insufficiency. These results indicate that the 2 weeks of IL-2 c.i. provided conditions enabling the harvest of large quantities of mononuclear cells from the peripheral blood of patients; this could be useful for future trials requiring the use of in vitro activated lymphocytes. Nevertheless, these pilot data suggest that this regimen of prolonged t.i.d. IL-2 administration after the LAK infusion does not seem to generate any improvement in antitumor effects from those obtained using other LAK + IL-2 regimens.

Adult↗
PubMed1993

Activation of multiple effector mechanisms to enhance tumor immunotherapy.

Recent technical advances have enabled the generation of clinical reagents for immunotherapy. Currently, treatment protocols combining both interleukin-2 (IL-2) and tumor-specific monoclonal antibody are underway at the University of Wisconsin Comprehensive Cancer Center and elsewhere. These approaches are based on the hypothesis that IL-2-activated lymphocytes will use tumor-reactive antibody to more selectively and effectively destroy tumor in vivo. Just as IL-2 can activate lymphocytes to destroy antibody-coated tumor cells, other agents can activate neutrophils and monocytes to destroy antibody-treated tumor cells. We are investigating, in laboratory and clinic, approaches aimed at eventually using combinations of distinct antibody-based tumor recognition mechanisms in patients whose monocytes, neutrophils, and lymphocytes have been simultaneously activated with multiple biologic agents.

Animals↗
PubMed1992

Serum CD25 levels during interleukin-2 therapy: dose dependence and correlations with clinical toxicity and lymphocyte surface sCD25 expression.

Using an enzyme-linked immunosorbent assay (ELISA), we have measured serum levels of a soluble form of the p55 subunit of the interleukin-2 receptor complex, soluble CD25 (sCD25), at regular intervals in the sera of 51 pediatric and adult cancer patients receiving recombinant human interleukin-2 (IL-2). The IL-2 was administered in repetitive weekly cycles alone or in combination with lymphokine-activated killer (LAK) cells. Levels of CD25 correlated with clinical toxicities reflected by nadir blood pressures, percentages of weight gained, and minimum Karnofsky performances during IL-2 therapy. Coadministration of autologous in vitro activated LAK cells together with IL-2 did not significantly affect the pattern of sCD25 release relative to administration of IL-2 alone. Examination of sCD25 release in response to different doses of IL-2 revealed a statistically significant dose effect of IL-2 on the sCD25 levels in patient sera. In addition, the level of sCD25 in patient sera also correlated strongly with expression of CD25 on the surface of peripheral blood lymphocytes (PBL) obtained from patients following IL-2 therapy. These studies demonstrate the utility of the sCD25 ELISA as a clinical tool for monitoring patients on treatment regimens that include IL-2.

Antigens, CD↗
PubMed1991

In vivo effects of multiple cycles of recombinant interleukin-2 (IL2) on peripheral granulocyte-macrophage hematopoietic progenitors circulating in the blood of cancer patients.

The numbers of peripheral blood (PB) granulocyte-macrophage colony forming units (CFU-GM) were evaluated in five patients treated with multiple weekly cycles of recombinant interleukin-2 (IL2). A 4.5-12 fold increase in the number of CFU-GM was evident within 8 days after the beginning of the treatment. The maximal increase in the absolute numbers of CFU-GM/ml blood caused by the IL2 treatment, ranged from 14 to 57 times the baseline values and was reached after two or three cycles of IL2. IL2-activated PBMC, added in vitro to the PBMC of a normal donor did not modify the number of CFU-GM present in the donor PBMC. CFU-GM were also recovered from frozen samples of in vivo IL2-activated PBMC.

Drug Administration Schedule↗
PubMed1991

Analysis of T cell receptor beta and gamma genes from peripheral blood, regional lymph node and tumor-infiltrating lymphocyte clones from melanoma patients.

A total of 199 T cell clones from two melanoma patients were derived from progenitor T cells from recurrent melanoma, regional lymph nodes (either involved or uninvolved with malignancy) and peripheral blood by inoculating single cells directly into the wells of microtiter plates before in vitro expansion. The surface marker phenotype of most clones was CD4+CD8-, although some were CD4-CD8+. Genomic DNA prepared from all clones was analyzed by Southern blot hybridization using T cell receptor (TCR) beta and gamma gene probes, seeking clones with identical TCR gene rearrangement patterns as direct evidence for in vivo progenitor T cell clonal amplification. Probing HindIII-digested DNA with TCR beta and TCR gamma probes revealed several clones with identical TCR gene rearrangement patterns. These clones had subsequent probing of BamHI-digested DNA with TCR beta and TCR gamma probes, which showed all but 2 clones to have distinct rearrangement patterns. These analyses provide clear molecular evidence for in vivo polyclonal CD4+ T cell populations in each of several separate immune compartments in these patients.

Adult↗
PubMed1991

BLT-esterase activity following in vitro and in vivo activation of human lymphocytes with interleukin-2. In vivo IL-2 induces BLT-esterase.

BLT-esterase and cytolytic activity by human in vitro and in vivo generated Lymphokine Activated Killer (LAK) cells were measured. Lysates made from peripheral blood lymphocytes (PBL) of both normal donors and cancer patients receiving IL-2 therapy were assayed for BLT-esterase activity in a spectro-photometric assay. Cytotoxicity of PBL was measured in a 51Cr-release assay. Both BLT-esterase activity and cytotoxicity increased when normal-donor PBL were stimulated in vitro with IL-2, with greater activities at higher IL-2 concentrations. The activities also increased over time, peaking at 6 days of in vitro stimulation. Patient PBL had increased BLT-esterase and cytotoxic activities after 4 weeks of in vivo IL-2 treatment. This association of BLT-esterase activity and cytotoxicity with IL-2 activation is consistent with the model that LAK cytotoxicity is mediated by secretion of BLT-esterase associated cytolytic granules. Lymphocytes obtained after in vivo IL-2 treatment and cultured for 3-4 hours in IL-2 show markedly augmented cytotoxic activity but no increase in their BLT-esterase activity. These results indicate that the increased cytotoxicity observed after this brief pulse of in vitro IL-2 following in vivo IL-2 treatment must result from effects of IL-2 other than the production of more esterase-containing cytolytic granules.

Cell Survival↗
PubMed1991

Activation of human T cells obtained pre- and post-interleukin-2 (IL-2) therapy by anti-CD3 monoclonal antibody plus IL-2: implications for combined in vivo treatment.

The role of activated T cells in the mediation of antitumor responses has been documented in several experimental models. In some of these, interleukin-2 (IL-2) has been used as a means to induce and expand the antitumor effects of the T cells. IL-2 has been tested in clinical trials for cancer treatment. Surprisingly, T cells appear to be inactivated by IL-2 in these clinical trials. T cells obtained from peripheral blood after IL-2 therapy showed decreased responses to mitogens and alloantigens, did not proliferate in vitro in response to IL-2, and did not mediate non-major histocompatibility complex-restricted cytotoxicity or targeted lysis in the presence of bispecific monoclonal antibodies. In this study, we present evidence that these post-IL-2 therapy T cells are not irreversibly inactivated; they can be activated in vitro by anti-CD3 monoclonal antibody together with IL-2 to upregulate the p55 component of the IL-2 receptor and proliferate. Nevertheless, following activation by anti-CD3 and IL-2, the level of targeted T-cell cytotoxicity mediated by the post-IL-2 therapy T cells was significantly lower than that by pre-IL-2 therapy T cells. Although in vivo treatment with IL-2 alone induces natural killer (NK) cells to mediate lymphokine-activated killer activity, these data suggest that the T-cell lytic function is inhibited by this treatment and only partially reversible by subsequent T-cell receptor activation using anti-CD3 mAb. Exposure of T cells to anti-CD3 mAb prior to in vivo IL-2 treatment generates T-cell lytic activity in vitro. These results, together with preclinical murine studies, suggest that a combined in vivo protocol of anti-CD3 mAb and IL-2, starting first with the anti-CD3 mAb, may cause activation of the T cells in addition to the activation of NK cells and thus warrant clinical testing.

Antibodies, Monoclonal↗
PubMed1991

Immunological effects of levamisole in vitro.

Levamisole, an anthelminthic drug with immunological properties, has recently been reported to have antitumor activity when administered with 5-fluorouracil in patients with Duke's C colorectal carcinoma. The mechanism of this antitumor effect is unknown, but has been postulated to be related to levamisole's immunomodulatory properties. To define further the immunomodulatory activities of levamisole, we studied the in vitro effects of levamisole on monocyte and lymphocyte cytotoxicity, activation, and proliferation; induction of cytokine-induced proteins; and expression of tumor-associated antigens. Experiments utilized peripheral blood mononuclear cells from normal donors incubated in the presence of increasing concentrations of levamisole (0.1 to 100 micrograms/ml). Levamisole had no consistent effect on induction of 2',5'-oligoadenylate synthetase activity or indoleamine-2,3-dioxygenase activity, or production of tumor necrosis factor. Levamisole had no effect on monocyte cytotoxicity or expression of HLA-DR, HLA-DQ, HLA-DP, and the Fc receptor. Similarly, levamisole had no significant effect on NK or LAK cytotoxicity or the immunological activation of T-lymphocytes, assessed by expression of CD3, CD4, CD8, CD16, CD25, and CD56. Proliferation of lymphocytes from normal donors, patients with benign polyps, and patients with malignancies, with or without IL-2 or irradiated LS174T cells, was not significantly increased overall. No significant enhancement in the expression of three tumor-associated antigens (880364, NRCO-4, and ING-1) and the intercellular adhesion molecule-1 (ICAM-1) antigen on four human cancer cell lines was observed following in vitro exposure to levamisole. We conclude that levamisole is not a potent modulator of the immune parameters we examined, and that the mechanism behind the unique clinical interaction between levamisole and 5-fluorouracil in colorectal carcinoma remains to be identified.

2',5'-Oligoadenylate Synthetase↗
PubMed1991

Prolonged interleukin-2 (IL-2) treatment can augment immune activation without enhancing antitumor activity in renal cell carcinoma.

Preliminary studies involving small numbers of patients have suggested that interleukin-2 (IL-2) administered by continuous infusion in repetitive weekly cycles using doses of 3 x 10(6) U/M2/day is immunologically active and can induce tumor responses in patients with renal cell carcinoma. This study was designed to examine both the immunological and clinical effects of prolonged infusion IL-2 given by repetitive weekly cycles; first at moderate doses for 4 weeks as an impatient followed by lower doses of IL-2 for up to 5 months. Prolonged IL-2 treatment was investigated because previous studies revealed that patients had a return to their baseline immune status within 4 weeks after completing IL-2 treatment. Twenty-five patients (including 18 with renal cell carcinoma) were treated with one of two regimens utilizing IL-2 as sole therapy. These regimens were designed to induce augmented and prolonged immune activation based upon in vitro and in vivo data. Though patients on both arms of the study demonstrated sustained lymphocytosis, increase in numbers of natural killer cells, and induction of lymphokine-activated killer activity with prolonged IL-2 administration, only 1 out of the 18 patients with renal cell carcinoma demonstrated a sustained partial antitumor response to therapy. Furthermore, several patients demonstrated profound immune activation, without any evidence of tumor regression. The lack of clinical responses in these patients showing marked activation of LAK cytotoxicity suggests that other variables must also influence the likelihood of antitumor effects for patients receiving IL-2 therapy.

Adult↗
PubMed1990

The influence of autologous lymphokine-activated killer cell infusions on the toxicity and antitumor effect of repetitive cycles of interleukin-2.

Twenty patients with refractory malignancies were treated with a protocol evaluating the addition of ex vivo-activated autologous lymphokine-activated killer (LAK) cells to a clinically tolerable interleukin-2 (IL-2) regimen (four weekly cycles of human recombinant IL-2 at 3 x 10(6) U/m2/day by continuous infusion for 4 days/week). Sixteen patients completed their induction month of therapy, two had a partial response, six had stable disease, and eight had progressive disease. Four patients had clinical toxicity preventing completion of the induction month of therapy, and one of these patients died during therapy. Significant clinical toxicities included decreased performance status, weight gain, catheter-related thromboses, infectious complications, fever, hypotension, and dyspnea or hypoxemia requiring oxygen. Thus, the addition of LAK cell infusions to this IL-2 regimen did not cause a noticeable change in antitumor response rate but did not cause more severe toxicity.

Adult↗