Drug Targeting Organ-Specific Strategies

1.5 Vaccination Strategies for Enhanced Immunity 15
methotrexate, and the general aim of these conjugates is to lower the (dose-limiting cardio-)
toxicity of these drugs. Enhanced permeability retention of the conjugates at the site of the
tumour is most likely the basis of local accumulation. In the studies reported, some objective
clinical responses were seen without concomitant toxicity of the drugs (Table 1.3). Although
the clinical responses until now seem rather disappointing, one should realize that the patients
who undergo clinical testing with these conjugates often carry large tumour burdens
which have been non-responsive towards other therapies available.
Table 1.3. Overview of recently reported clinical studies with miscellaneous drug targeting strategies.
Carrier Drug Disease Clinical Remarks c
incorporated response a,b
Antibody
90
Y Metastatic 2/25 OR Pre-targeted strategy: [91]
colon cancer 2/25 PR mAb NR-LU-10 –
4/25 SD streptavidin, followed
by biotin-gal-HSA
clearing and biotin-
DOTA- 90 Y
Non-Hodgkin 3/7 CR Pre-targeted strategy: [92]
lymphoma 1/7 PR mAb Rituximab –
2/7 OR streptavidin, followed
by biotin-N-acetylgalactosamine
clearing
and biotin-DOTA90Y HPMA Doxorubicin Various 2/36 PR Clinical proof of
copolymer malignancies 2/36 MR principle of decrease [15]
(PK1) of doxorubicin toxicity
when polymer bound
Poly(styrene- Neocar- Renal cell Improved survival, SMANCS dissolved in [93]
co-maleic acid) zinostatin carcinoma depending on lipiodol contrast
polymers patients tumour size medium, administered
(SMANCS) via the renal artery
Human serum Methotrexate Cancer patients 17 patients: 1 PR [94]
albumin and 1 MR in RCC
patients; 1 MR in
pleural mesothelioma
patient
1.5 Vaccination Strategies for Enhanced Immunity
Reference
a Number of patients responding/total number of evaluable patients. CR, complete remission/response;
PR, partial response; MR, minor response; OR, objective response; SD, stable disease.
b RCC, renal cell carcinoma.
c mAb, monoclonal antibody.
Vaccination can be considered as a therapeutic modality that actively engages the immune
system of the patient. It encompasses numerous principles derived from drug targeting research.
Modification of the responses of the immune system may be an effective approach to
improve the disease status of patients with a variety of diseases. Either prevention of au-