Advances in the biological approach to cancer therapy are reviewed. The mechanisms of actions, clinical effects and uses of interferons, the first biological modifiers to be used, are reviewed first. The interleukins and monoclonal antibodies are also mentioned in detail. This review also covers the clinical use and production of lymphokine activated killer cells, which are used in conjunction with interleukin-2. A brief review of tumour infiltrating lymphocytes, which comprise a subset of lymphocytes found within solid tumours is given. In mice, tumour infiltrating lymphocytes have been shown to be more therapeutic than lymphokine activated killer cells. Tumour necrosis factor, a protein released by activated macrophages in response to stimulation by endotoxin, is also briefly mentioned although clinical data are disappointing. Finally, the role which oncogenes may play in cancer therapy and understanding is discussed.
IsaacsALindemannJJ: Virus interference: the interferon. Proc R Soc Lond (Biol)1957; 147: 258–267.
2.
FaltynekCROppenheimJJ: J Natl Cancer Inst80: 151–153.
3.
DerunckRContentJDe ClerqE: Isolation and structure of a human fibroblast interferon gene. Nature1980; 285: 542–549.
4.
SehgalPB: The interferon gene. Biochim Biophys Acta1982; 695: 17–33.
5.
EvingerMRubinsteinMPestkaS: Antiproliferative and antiviral activities of human leukocyte interferons. Arch Biochem Biophys1981; 210: 319–329.
6.
BaronSBlalockJEDianzaniF: Immune interferon: some properties and functions. Ann NY Acad Sci1980; 350: 130–144.
7.
BalkwillFR: The regulatory role of interferons in the human immune response. In: Interferons and Impact in Biology and Medicine (Taylor-PapadimitriouJ, ed). Oxford: Oxford Medical Publications, 1985; pp 61–62.
8.
BalkwillFRSmythJF: Interferons in cancer therapy: a reappraisal. Lancet1987; ii: 317–319.
9.
ErnstoffMSFusiSRudnickS: Parameters of interferon action. II. Immunological effects of recombinant leukocyte interferon in phase I – II trials. J Biol Response Mod1983; 2: 540–547.
10.
ScottGMSecherDSFlowersD: Toxicity of interferon. Br Med J1981; 282: 1345–1348.
11.
SmedleyHMWheelerTK: The toxicity of interferon. In: Interferon and Cancer (SikoraK, ed). New York: Plenum Press, pp 136–142.
12.
ClemensM: Interferons and oncogenes. Nature1985; 313: 531–532.
13.
StranderHCantellKIngimarsonS: Interferon treatment of osteogenic sarcoma: a clinical trial. Conference on Modulation of Host Immune Resistance on the Prevention and Treatment of Induced Neoplasias. Washington DC: US Government Printing Office, 1974; 28: 377–381.
14.
ItoHMurakamiKYanagawaT: Effect of human leukocyte interferon on the metastatic lung tumour of osteosarcoma. Cancer1980; 46: 1562–1565.
15.
LouieACGallagherJGSikoraK: Follow-up observations on the effect of human leukocyte interferon in non-Hodgkin's lymphoma. Blood1981; 58: 712–718.
16.
LeavittRDRatanatharathornVOzerH: A phase II study of recombinant alpha-2 interferon in patients with malignant lymphoma with unfavourable histology. Proc Am Soc Clin Oncol1983; 2: 54.
17.
MellstedtH: Human leukocyte interferon (IFN alpha) in the treatment of multiple myeloma. Antiviral Res1983; 1: 36.
18.
MandelliFTribaltoMAvvisatiG: Recombinant interferon alpha-2b (Intron) as post-induction therapy for responding multiple myeloma patients. M84 protocol. Cancer Treat Rev1981; 15 (suppl A): 43–48.
19.
SilverHKBConnorsJSalinasF: Treatment response in a prospectively randomised study of high versus low dose treatment with lymphoblastoid interferon (IFN). Proc Am Soc Clin Oncol1983; 2: 51.
20.
LeghaSS: Interferons in the treatment of malignant melanoma. A review of recent trials. Cancer1986; 57: 1675–1677.
21.
MichaleviczRRevelM: Interferons regulate the in vitro differentiation of multilineage lympho-myeloid stem cell in hairy-cell leukaemia. Proc Natl Acad Sci USA1987; 84: 2307–2311.
22.
QuesadaJRHershEMGuttermanJU: Hairy-cell leukaemia. Induction of remission with alpha interferon. Blood1983; 62: 207a.
23.
QuesadaJRSwansonDATrindadeA: Renal cell carcinoma: anti-tumour effects of leukocyte interferon. Cancer Res1983; 43: 940–947.
24.
NethersellASikoraK: Interferons and malignant disease. In: Interferons and Impact in Biology and Medicine (Taylor-PapadimitriouJ, ed). Oxford: Oxford Medical Publications, 1985; pp 61–62.
25.
SternJBSmithKA: IL-2 induction of G1 progression and c-myb expression. Science1986; 233: 203–206.
26.
KornfeldHBermanJSBeerDJ: Induction of human T-lymphocyte motility by IL-2. J Immunol1985; 134: 3887–3890.
27.
LeeKO'DonnellRWCockettAT: Ineffectiveness of adoptive chemoimmunotherapy with lympho-kine-activated killer cells, interleukin-2, and cyclophosphamide on palpable intradermal murine bladder cancer. J Biol Response Mod1988; 7: 43–55.
28.
RosenbergSALotzeMTMuulLM: Observations on the systemic administration of autologous lymphokine-activated killer cell and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med1985; 313: 1485–1492.
29.
RosenbergSALotzeMTMuulLM: A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med1987; 316: 889–897.
30.
RosensteinMEttinghausenSERosenbergSA: Extravasation of intravascular fluid mediated by the systemic administration of recombinant interleukin-2 appears to occur in humans, as measured by albumin excretion. J Immunol1986; 137: 1735–1742.
31.
LeeRELotzeMTSkibberJM: Cardiorespiratory effects of immunotherapy with interleukin-2. J Clin Oncol1989; 7: 7–20.
32.
OsantoSCluitmansFHFranksCR: Myocardial injury after interleukin-2 therapy. Lancet1988; ii: 48–49.
33.
WestWHTauerKWYannelliJR.: Constant infusion recombinant interleukin-2 in adoptive immunotherapy of advanced cancer. N Engl J Med1987; 316: 898–905.
34.
RosenbergSAPackardBSAebersoldPM: Use of tumour-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma: a preliminary report. N Engl J Med1988; 319: 1676–1680.
35.
LiuSJAscensaoJLPodackE: Cellular interactions in haemopoiesis. Blood-Cells1987; 13: 101–110.
36.
MitchellMSKempfRAHarelW: Effectiveness and tolerability of low dose cyclophosphamide and low-dose intravenous interleukin-2 in disseminated melanoma. J Clin Oncol1988; 6: 409–424.
37.
AgahRMalloyBSherrodA: Therapy of disseminated NK resistant tumour by the synergistic effects of recombinant interleukin-2 and tumour necrosis factor. J Biol Response Mod1988; 7: 140–151.
38.
MelioliGBaldiniEDe MariaA: Intraperitoneal infusion of interleukin-2 in patients with malignant ascites: phenotypic and functional effects on tumour-associated lymphocytes. Ric Clin Lab1988; 18: 61–66.
39.
TopalianSLRosenbergSA: Therapy of cancer using the adoptive transfer of activated killer cells and interleukin-2. Acta Haematol1987; 78 (suppl 1): 75–76.
40.
KimotoYTaguchiT: Adoptive immunotherapy of malignant diseases with IL-2 activated lymphocytes. Biken J1987; 30: 29–38.
41.
OchoaACMiglioriRJAlterBJ: Long-term culture of LAK cells: expansion and activation signals. Prog Clin Biol Res1987; 244: 289–299.
42.
SaitoTTanakaRYoshidaS: Immunohistochemical analysis of tumour-infiltrating lymphocytes and major histocompatibility antigens in human gliomas and metastatic brain tumours. Surg Neurol1988; 29: 435–442.
43.
TopalianSSolomonDAvisFP: Immunotherapy of patients with advanced cancer using tumour-infiltrating lymphocytes and recombinant interleukin-2: a pilot study. J Clin Oncol1988; 6: 839–853.
44.
CohenPJLotzeMTRobertsJR: The immunopathology of sequential tumour biopsies in patients treated with interleukin-2. Correlation of response with T-cell infiltration and HLA-DR expression. Am J Pathol1987; 129: 208–216.
45.
GrayPWAggarwalWBentonB: Cloning and expression of c-DNA for human lymphotoxin. Nature1984; 312: 721–729.
46.
SelbyPHobbsSVinerC: Tumour necrosis factor in man: clinical and biological observations. Br J Cancer1987; 56: 803–808.
47.
KohlerGMilsteinC: Continuous cultures of fused cells secreting antibody of predefined specificity. Nature1975; 256: 495–497.
48.
BobrowLGNortonAJ: Immunohistology in the identification of tumour types. Cancer Surv1987; 6: 209–225.
49.
Van DuinenSGRuiterDGHagemanP: Immunohistochemical and histochemical tools in the diagnosis of amelanotic melanoma. Cancer1984; 53: 1566–1573.
50.
BegentRHJGreenAFBagshaweKD: Liposomally entrapped second antibody improves tumour imaging with radiolabelled (first) antitumour antibody. Lancet1982; ii: 739–742.
51.
RiechmenLClarkMWaldmannH: Reshaping human antibodies for therapy. Nature1988; 332: 323–327.
52.
HaleGDyerMJSClarkMR: Remission induction in non-Hodgkin's lymphoma with reshaped human monoclonal antibody CAM-PATH-1H. Lancet1988; ii: 1394–1399.
53.
KalofonosHPStewartJSWEpenetosAA: Antibody-guided diagnosis and therapy of malignant lesions. Int J Cancer1988; 2 (suppl): 74–80.
54.
BagshaweKDSpringerCJSearleF: A cytotoxic agent can be generated selectively at cancer sites. Br J Cancer1988; 58: 700–703.
55.
ChanSSikoraK: The potential of oncogene products as tumour markers. Cancer Surv1987; 6: 185–207.
56.
SainsburyJRCFaradenJRNeedhamGK: Epidermal growth factor receptor status as predictor of early recurrence and death from breast cancer. Lancet1987; i: 1398–1402.
